Elagolix

Elagolix is a GnRH receptor antagonist that inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland. Administration of ORILISSA results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones, estradiol and progesterone.


ERAVACYCLINE

Eravacycline is a fluorocycline antibacterial within the tetracycline class of antibacterial drugs. Eravacycline disrupts bacterial protein synthesis by binding to the 30S ribosomal subunit thus preventing the incorporation of amino acid residues into elongating peptide chains.


Doravirine

Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor of HIV-1 and inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT). Doravirine does not inhibit the human cellular DNA polymerases alpha, beta, and mitochondrial DNA polymerase gamma.


Duvelisib

Duvelisib is an inhibitor of PI3K with inhibitory activity predominantly against PI3K-delta and PI3K-gamma isoforms expressed in normal and malignant B-cells. Duvelisib induced growth inhibition and reduced viability in cell lines derived from malignant B-cells and in primary CLL tumor cells. Duvelisib inhibits several key cell-signaling pathways, including B-cell receptor signaling and CXCR12-mediated chemotaxis of malignant B-cells. Additionally, duvelisib inhibits CXCL12-induced T cell migration and M-CSF and IL-4 driven M2 polarization of macrophages.


SARECYCLINE

The mechanism of action of sarecycline in treating acne vulgaris is not known.


Omadacycline

Omadacycline is an aminomethylcycline antibacterial within the tetracycline class of antibacterial drugs.  Omadacycline binds to the 30S ribosomal subunit and blocks protein synthesis.  Omadacycline is active in vitro against Gram positive bacteria expressing tetracycline resistance active efflux pumps (tetK and tet L) and ribosomal protection proteins (tet M).  In general, omadacycline is considered bacteriostatic; however, omadacycline has demonstrated bactericidal activity against some isolates of S. pneumoniae and H. influenzae.


Talazoparib

Talazoparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1 and PARP2, which play a role in DNA repair. In vitro studies with cancer cell lines that harbored defects in DNA repair genes, including BRCA 1 and 2, have shown that talazoparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, decreased cell proliferation, and apoptosis. Talazoparib anti-tumor activity was observed in human patient-derived xenograft breast cancer tumor models that expressed mutated or wild-type BRCA 1 and 2.


Germline BRCA-mutated, HER2-negative metastatic breast cancer

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Dacomitinib

Dacomitinib is an irreversible inhibitor of the kinase activity of the human EGFR family (EGFR/HER1, HER2, and HER4) and certain EGFR activating mutations (exon 19 deletion or the exon 21 L858R substitution mutation). In vitro dacomitinib also inhibited the activity of DDR1, EPHA6, LCK, DDR2, and MNK1 at clinically relevant concentrations.

A member of the class of quinazolines that is 7-methoxyquinazoline-4,6-diamine in which the amino group at position 4 is substituted by a 3-chloro-4-fluorophenyl group and the amino group at position 6 is substituted by an (E)-4-(piperidin-1-yl)but-2-enoyl group.


Lorlatinib

Lorlatinib is a kinase inhibitor with in vitro activity against ALK and ROS1 as well as TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors.

A cyclic ether that is 16,17-dihydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecin-15(10H)-one substituted by methyl groups at positions 2 and 10R, and by cyano, amino and fluoro groups at positions 3, 7 and 12 respectively. It is a small molecule inhibitor of ALK and ROS1 kinase developed by Pfizer for the treatment of ALK-positive non-small cell lung cancer.


Revefenacin

Revefenacin is a long-acting muscarinic antagonist, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo models, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of revefenacin is predominantly a site-specific effect.


Glasdegib

Glasdegib is an inhibitor of the Hedgehog pathway. Glasdegib binds to and inhibits Smoothened, a transmembrane protein involved in hedgehog signal transduction.

A member of the class of benzimidazoles that is 1H-benzimidazole which is substituted by a (2R,4S)-4-{[(4-cyanophenyl)carbamoyl]amino}-1-methylpiperidin-2-yl group at position 2. It is a hedgehog signalling pathway inhibitor that acts by binding to Smoothened (SMO) receptors and blocking signal transduction (IC50 = 5 nM). It is used in combination with low-dose cytarabine, for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adult patients (aged >= 75 years), or who have medical conditions that prevent the use of standard chemotherapy.


Gilteritinib

Gilteritinib is a small molecule that inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3). Gilteritinib demonstrated the ability to inhibit FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells expressing FLT3-ITD.

A member of the class of pyrazines that is pyrazine-2-carboxamide which is substituted by {3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}nitrilo, (oxan-4-yl)nitrilo and ethyl groups at positions 3,5 and 6, respectively. It is a potent inhibitor of FLT3 and AXL tyrosine kinase receptors (IC50 = 0.29 nM and 0.73 nM, respectively). Approved by the FDA for the treatment of acute myeloid leukemia in patients who have a FLT3 gene mutation.


Evocalcet

Evocalcet is a new type of oral calcimimetics agent. The drug suppresses parathyroid hormone secretion by acting on the calcium receptors on parathyroid gland cells.


Rifamycin

A member of the class of rifamycins that exhibits antibiotic and antitubercular properties.


Triclabendazole

Benzimidazole antiplatyhelmintic agent that is used for the treatment of FASCIOLIASIS and PARAGONIMIASIS.


fascioliasis

A parasitic infection that is caused by liver flukes, usually Fasciola hepatica, of sheep, goats, and cattle. Humans become infected by eating uncooked, infested aquatic vegetation (classically watercress). adult flukes inhabit the bile ducts, gallbladder, and occasionally ectopic sites. Symptoms arise secondary to inflammatory response or obstruction.


ATTRV122I amyloidosis

Transthyretin (TTR)-related familial amyloidotic cardiomyopathy is a hereditary TTR-related systemic amyloidosis (ATTR) with predominant cardiac involvement resulting from myocardial infiltration of abnormal amyloid protein.


brexanolone

Brexanolone is a neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator indicated for the treatment of postpartum depression (PPD) in adults.


Solriamfetol

The mechanism of action of solriamfetol to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea is unclear. However, solriamfetol binds to the dopamine transporter and norepinephrine transporter with low affinity and inhibits the reuptake of dopamine and norepinephrine with low potency. Solriamfetol has no appreciable binding affinity for the serotonin transporter (Ki=81.5 μM) and does not inhibit serotonin reuptake (IC50 > 100 μM). Solriamfetol improves wakefulness in patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea is unclear. However, its efficacy could be mediated through its activity as a dopamine and norepinephrine reuptake inhibitor (DNRI).


Excessive daytime sleepiness - normal night sleep

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obstructive sleep apnea syndrome

Cessation of air flow during sleep due to upper airway obstruction.


Siponimod

Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator. Siponimod binds with high affinity to S1P receptors 1 and 5. Siponimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which siponimod exerts therapeutic effects  in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system.


Alpelisib

Alpelisib is an inhibitor of phosphatidylinositol-3- kinase (PI3K) with inhibitory activity predominantly against PI3Kalpha. Gain-of-function mutations in the gene encoding the catalytic alpha-subunit of PI3K (PIK3CA) lead to activation of PI3Kalpha and Akt-signaling, cellular transformation and the generation of tumors in in vitro and in vivo models.


Bremelanotide

Bremelanotide is a melanocortin receptor (MCR) agonist that nonselectively activates several receptor subtypes with the following order of potency: MC1R, MC4R, MC3R, MC5R, MC2R. The mechanism by which VYLEESI improves HSDD in women is unknown. The MC1R is expressed on melanocytes; binding at this receptor leads to melanin expression and increased pigmentation


PRABOTULINUMTOXIN A

PrabotulinumtoxinA-xvfs is an acetylcholine release inhibitor and a neuromuscular blocking agent


Rhytidectomy of glabellar frown lines

biolink:Procedure biolink:NamedThing biolink:Entity biolink:ActivityAndBehavior biolink:Occurrent biolink:PhysicalEssenceOrOccurrent


ONASEMNOGENE ABEPARVOVEC

ZOLGENSMA is a recombinant AAV9-based gene therapy designed to deliver a copy of the gene encoding the human SMN protein. SMA is caused by a bi-allelic mutation in the SMN1 gene, which results in insufficient SMN protein expression. Intravenous administration of ZOLGENSMA that results in cell transduction and expression of the SMN protein has been observed in two human case studies


CAPLACIZUMAB

In patients with aTTP, levels of a substance called von Willebrand factor are increased. von Willebrand factor acts on platelets to cause them to stick together and form blood clots. Caplacizumab, the active substance in Cablivi, is a nanobody (a small antibody) which has been designed to attach to von Willebrand factor in a way that stops it acting on platelets. This reduces platelets sticking together and forming clots in blood vessels and, as a result, platelet levels in the blood rise because they are no longer taken up to form clots.


LANADELUMAB

Lanadelumab-flyo is a fully human monoclonal antibody (IgG1/kappa-light chain) that binds plasma kallikrein and inhibits its proteolytic activity. Plasma kallikrein is a protease that cleaves high-molecular-weight-kininogen (HMWK) to generate cleaved HMWK (cHMWK) and bradykinin, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE.In patients with HAE due to C1-inhibitor (C1-INH) deficiency or dysfunction, normal regulation of plasma kallikrein activity is not present, which leads to uncontrolled increases in plasma kallikrein activity and results in angioedema attacks. Lanadelumab-flyo decreases plasma kallikrein activity to control excess bradykinin generation in patients with HAE.


CONDOLIASE

Condoliase degrades chondroitin sulfate, chondroitin, and hyaluronic acid and also improves the clinical manifestations of herniation by lowering the internal pressure of the intervertebral disc due to dissolving the glycosaminoglycans within the nucleus pulposus of the intervertebral disc, and lowering the water-holding capacity of the nucleus pulposus.


Vibegron

Vibegron is selectively binds to the beta 3 adrenergic receptor (beta3 AR) in bladder smooth muscle, resulting in relaxation of the detrusor muscle.

A pyrrolopyrimidine obtained by formal condensation of the carboxy group of (6S)-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6-carboxylic acid with the amino group of (R)-[(2R,5S)-5-(4-aminobenzyl)pyrrolidin-2-yl](phenyl)methanol. It is a beta3-adrenergic receptor agonist currently in clinical development for the treatment of patients with overactive bladder.


Omidenepag isopropyl

Omidenepag isopropyl is a prodrug that is converted by hydrolysis to omidenepag, the active form that it is thought to lower ophthalmic pressure via a dual mechanism of action, increasing both the trabecular outfow facility and the uveoscleral outfow as a result of EP2 receptor stimulation, thereby promoting aqueous outfow.


PATISIRAN

Patisiran is a double-stranded siRNA that causes degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.


Amyloid Neuropathies

Neuropathy caused by amyloid deposition in the peripheral nerves.


Moxetumomab pasudotox-tdfk is a CD22-directed cytotoxin. Moxetumomab pasudotox-tdfk binds CD22 on the cell surface of B-cells and is internalized. Moxetumomab pasudotox -tdfk internalization results in ADP-ribosylation of elongation factor 2, inhibition of protein synthesis, and apoptotic cell death.


FREMANEZUMAB

Fremanezumab-vfrm is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor.


GALCANEZUMAB

Galcanezumab-gnlm  is a humanized  monoclonal  antibody that  binds to calcitonin gene-related  peptide (CGRP)  ligand and blocks its binding to the receptor.


CEMIPLIMAB

Cemiplimab-rwlc is a recombinant human immunoglobulin G4 (IgG4) monoclonal antibody that binds to PD-1 and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.


Elapegademase

Elapegademase-lvlr provides an exogenous source of ADA enzyme that is associated with a decrease in toxic adenosine and deoxyadenosine nucleotides levels as well as an increase in lymphocyte number.


Inotersen

Inotersen is an antisense oligonucleotide that causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.


familial hemophagocytic lymphohistiocytosis type 1

Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare primary immunodeficiency characterized by a macrophage activation syndrome with an onset usually occurring within a few months or less common several years after birth.


RAVULIZUMAB

Ravulizumab-cwvz is a terminal complement inhibitor that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a (the proinflammatory anaphylatoxin) and C5b (the initiating subunit of the terminal complement complex [C5b-9]) and preventing the generation of the terminal complement complex C5b9. ULTOMIRIS inhibits terminal complement-mediated intravascular hemolysis in patients with PNH.


meningococcal infection

Infections with bacteria of the species neisseria meningitidis.


TAGRAXOFUSP

Tagraxofusp-erzs is a CD123-directed cytotoxin composed of recombinant human interleukin-3 (IL-3) and truncated diphtheria toxin (DT) fusion protein that inhibits protein synthesis and causes cell death in CD123-expressing cells.


CD4+/CD56+ hematodermic neoplasm

An aggressive immature hematologic neoplasm formerly known as blastic NK cell lymphoma, composed of cells with a lymphoblast-like morphology. Recent evidence suggests derivation from a plasmacytoid monocyte. Patients present with cutaneous tumors and bone marrow involvement.


Larotrectinib

Larotrectinib is an inhibitor of the tropomyosin receptor kinases (TRK), TRKA, TRKB, and TRKC. In a broad panel of purified enzyme assays, larotrectinib inhibited TRKA, TRKB, and TRKC with IC50 values between 5-11 nM. One other kinase TNK2 was inhibited at approximately 100-fold higher concentration. TRKA, B, and C are encoded by the genes NTRK1, NTRK2, and NTRK3.Chromosomal rearrangements involving in-frame fusions of these genes with various partners can result in constitutively-activated chimeric TRK fusion proteins that can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines.


POLATUZUMAB VEDOTIN

Polatuzumab vedotin-piiq is a CD79b-directed antibody-drug conjugate with activity against dividing B cells. The small molecule, MMAE is an anti-mitotic agent covalently attached to the antibody via a cleavable linker. The monoclonal antibody binds to CD79b, a B-cell specific surface protein, which is a component of the B-cell receptor. Upon binding CD79b, polatuzumab vedotin-piiq is internalized, and the linker is cleaved by lysosomal proteases to enable intracellular delivery of MMAE. MMAE binds to microtubules and kills dividing cells by inhibiting cell division and inducing apoptosis


Darolutamide is an androgen receptor (AR) inhibitor. Darolutamide competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. A major metabolite, keto-darolutamide, exhibited similar in vitro activity to darolutamide. In addition, darolutamide functioned as a progesterone receptor (PR) antagonist in vitro (approximately 1% activity compared to AR). Darolutamide decreased prostate cancer cell proliferation in vitro and tumor volume in mouse xenograft models of prostate cancer


castration-resistant prostate carcinoma

A prostate carcinoma that is characterized by continued growth and spread despite the surgical removal of the testes or medical intervention to block androgen production.


Volanesorsen

Volanesorsen is an antisense oligonucleotide designed to inhibit the formation of apoC-III, a protein that is recognised to regulate both triglyceride metabolism and hepatic clearance of chylomicrons and other triglyceride-rich lipoproteins. The selective binding of volanesorsen to the apoC-III messenger ribonucleic acid (mRNA) within the 3′ untranslated region at base position 489-508 causes the degradation of the mRNA. This binding prevents translation of the protein apoC-III, thus removing an inhibitor of triglyceride clearance and enabling metabolism through an LPL-independent pathway


ANDEXANET ALFA

Andexanet alfa is a recombinant form of human FXa protein that has been modified to lack FXa enzymatic activity. The active site serine was substituted with alanine, rendering the molecule unable to cleave and activate prothrombin, and the gamma-carboxyglutamic acid (Gla) domain was removed to eliminate the ability of the protein to assemble into the prothrombinase complex, thus removing any anti-coagulant effects. Andexanet alfa is a specific reversal agent for FXa inhibitors. The predominant mechanism of action is the binding and sequestration of the FXa inhibitor, although there may be a minor contribution from the inhibition of tissue factor pathway inhibitor (TFPI) activity through binding to TFPI. The interaction between andexanet alfa and TFPI has not been fully characterized. Andexanet alfa binds direct FXa inhibitors with high affinity, making them unavailable to exert their anticoagulant effects


Direct acting anticoagulant adverse reaction


RISANKIZUMAB

Skyrizi is a medicine used to treat plaque psoriasis, a disease causing red, scaly patches on the skin. Indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy


Ropeginterferon ALFA-2B

Ropeginterferon alfa-2b is a recombinant interferon alfa-2b conjugated with a two-arm methoxypolyethylene glycol (mPEG). It belongs to the class of type I interferons which exhibit their cellular effects by binding to a transmembrane receptor termed interferon alfa receptor (IFNAR). Binding to IFNAR initiates a downstream signalling cascade through the activation of kinases, in particular Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2) and activator of transcription (STAT) proteins. Nuclear translocation of STAT proteins controls distinct gene-expression programs and exhibit various cellular effects. Interferon alfa was shown to have an inhibitory effect on the proliferation of hematopoietic and bone marrow fibroblast progenitor cells and antagonised the action of growth factors and other cytokines that have a role in the development of myelofibrosis. These actions may be involved in the therapeutic effects of interferon alfa in polycythaemia vera.Further, it was demonstrated that interferon alfa is able to decrease the mutated JAK2V617F allele burden in patients with polycythaemia vera (a V617F point mutation in the JAK2 kinase is a hallmark of polycythaemia vera and is  present in approximately 95% of patients)


Sotagliflozin

Sotagliflozin is a dual inhibitor of sodium glucose cotransporter type 1 (SGLT1) and SGLT2. Local intestinal inhibition of SGLT1, the major transporter for glucose absorption, delays and reduces glucose absorption in the proximal intestine, resulting in a blunting and delay of postprandial hyperglycaemia. SGLT2 is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. By inhibiting SGLT2, sotagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion


Pegvaliase

The active substance in Palynziq, pegvaliase, is a bacterial enzyme that can break down phenylalanine, thereby stopping phenylalanine from building up in the body and helping to relieve the symptoms of phenylketonuria. The enzyme in pegvaliase is ‘pegylated’ (attached to a chemical called PEG), allowing it to remain in the body and to act for longer


Quizartinib

Quizartinib is the most selective type II FLT3 inhibitor and has shown the strongest single-agent activity in patient population with R/R-AML (acute myeloid leukemia) with FLT3 mutations. The FLT3 tyrosine kinase inhibitors act as direct inhibitors of FLT3 via competitive inhibition of ATP-binding sites in the FLT3 receptor. Type II FLT3 inhibitors bind the FLT3 receptor in the inactive conformation in a region adjacent to the ATP-binding domain. As a result of this binding affinity, these inhibitors prevent activity of ITD (the internal tandem duplication) mutations but do not target TKD (the tyrosine kinase domain) mutations

A member of the class of phenylureas that is urea in which one of the amino groups has been substituted by a 5-tert-butyl-1,2-oxazol-3-yl group while the other has been substituted by a phenyl group substituted at the para- position by an imidazo[2,1-b][1,3]benzothiazol-2-yl group that, in turn, is substituted at position 7 by a 2-(morpholin-4-yl)ethoxy group.


Acute myeloid leukemia with FMS-like tyrosine kinase-3 mutation


Monoamine oxidase inhibitor (disposition)


fallopian tube neoplasm

A benign or malignant neoplasm affecting the fallopian tube. Representative examples of benign neoplasms include papilloma, adenofibroma, and leiomyoma. Representative examples of malignant neoplasms include carcinoma, carcinosarcoma, and adenosarcoma.


Esketamine

The S- (more active) enantiomer of ketamine.


Erdafitinib

Erdafitinib inhibited FGFR phosphorylation and signaling and decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions. Erdafitinib demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer.


Metastatic urothelial carcinoma

A carcinoma that arises from the urothelium and has spread from its original site of growth to another anatomic site.


Selinexor

Selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1(XPO1)


Pexidartinib

Pexidartinib is a small molecule tyrosine kinase inhibitor that targets colony stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring an internal tandem duplication (ITD) mutation. Overexpression of the CSF1R ligand promotes cell proliferation and accumulation in the synovium. In vitro, pexidartinib inhibited proliferation of cell lines dependent on CSF1R and ligand-induced autophosphorylation of CSF1R. Pexidartinib also inhibited the proliferation of a CSF1R dependent cell line in vivo.

A pyrrolopyridine that is 5-chloro-1H-pyrrolo[2,3-b]pyridine which is substituted by a [6-({[6-(trifluoromethyl)pyridin-3-yl]methyl}amino)pyridin-3-yl]methyl group at position 3. It is a potent multi-targeted receptor tyrosine kinase inhibitor of CSF-1R, KIT, and FLT3 (IC50 of 20 nM, 10 nM and 160 nM, respectively). Approved by the FDA for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT).


tenosynovial giant cell tumor

A tumor usually arising in the synovium of joints, bursa or tendon sheath. It is characterized by the presence of mononuclear cells, multinucleated osteoclast-like giant cells, hemosiderin-laden macrophages, foam cells, and an inflammatory infiltrate. According to the growth pattern, it is classified as localized or diffuse.


Pretomanid

Pretomanid Tablet is a nitroimidazooxazine antimycobacterial drug. Pretomanid kills actively replicating M. tuberculosis by inhibiting mycolic acid biosynthesis, thereby blocking cell wall production. Under anaerobic conditions, against non-replicating bacteria, pretomanid acts as a respiratory poison following nitric oxide release


extensively drug-resistant tuberculosis

A type of drug-resistant tuberculosis that is resistant to any fluoroquinolone, and at least one of three second-line injectable drugs (capreomycin, kanamycin, and amikacin), in addition to resistance to rifampicin and isoniazid.


Entrectinib

Entrectinib is an inhibitor of the tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, and TRKC (encoded by the neurotrophic tyrosine receptor kinase [NTRK] genes NTRK1, NTRK2, and NTRK3, respectively), proto-oncogene tyrosine-protein kinase ROS1 (ROS1), and anaplastic lymphoma kinase (ALK).


Reactive oxygen species 1 positive non-small cell lung cancer


Upadacitinib

Upadacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) which modulate intracellular activity including gene expression. Upadacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs.


Fedratinib

Fedratinib is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). Fedratinib is a JAK2-selective inhibitor with higher inhibitory activity for JAK2 over family members JAK1, JAK3 and TYK2. Abnormal activation of JAK2 is associated with myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera.


Lefamulin

XENLETA is a semi-synthetic antibacterial agent for oral and intravenous administration. Lefamulin inhibits bacterial protein synthesis through interactions (hydrogen bonds, hydrophobic interactions, and Van der Waals forces) with the A- and P-sites of the peptidyl transferase center (PTC) in domain V of the 23s rRNA of the 50S subunit. The binding pocket of the bacterial ribosome closes around the mutilin core for an induced fit that prevents correct positioning of tRNA.


Netspot

A radioconjugate consisting of the octreotide derivative edotreotide labeled with gallium 68 (Ga-68) with potential application in somatostatin receptor (SSTR) imaging in conjunction with positron emission tomography (PET). Similar to octreotide, gallium Ga 68-edotreotide binds to SSTRs, especially type 2 receptors, present on the cell membranes of many types of neuroendocrine tumor cells and their metastases, thereby allowing for imaging of SSTR-expressing cells upon PET. Gallium Ga 68-edotreotide is produced by substituting tyrosine for phenylalanine at the 3 position of the somatostatin analogue octreotide (Tyr3-octreotide or TOC) and chelating the substituted octreotide to Ga-68 via the macrocyclic chelating agent dodecanetetraacetic acid (DOTA).


Positron emission tomography with computed tomography of whole body using gallium (68-Ga) dotatate


Tenapanor

IBSRELA (tenapanor) tablets contain tenapanor hydrochloride as an active ingredient. Tenapanor hydrochloride is a sodium/hydrogen exchanger 3 (NHE3) inhibitor for oral use, an antiporter expressed on the apical surface of the small intestine and colon primarily responsible for the absorption of dietary sodium. In vitro and animal studies indicate its major metabolite, M1, is not active against NHE3. By inhibiting NHE3 on the apical surface of the enterocytes, tenapanor reduces absorption of sodium from the small intestine and colon, resulting in an increase in water secretion into the intestinal lumen, which accelerates intestinal transit time and results in a softer stool consistency.


Trifarotene

AKLIEF Cream for topical administration contains 0.005% (50 mcg/g) trifarotene. Trifarotene is a terphenyl acid derivative and is a retinoid. Trifarotene is an agonist of retinoic acid receptors (RAR), with particular activity at the gamma subtype of RAR. Stimulation of RAR results in modulation of target genes which are associated with various processes, including cell differentiation and mediation of inflammation. The exact process by which trifarotene ameliorates acne is unknown.


Lasmiditan

Reyvow (lasmiditan) is a serotonin (5-HT) 1F receptor agonist for oral administration, bindinding with high affinity to the 5-HT1F receptor. Lasmiditan presumably exerts its therapeutic effects in the treatment of migraine through agonist effects at the 5-HT1F receptor; however, the precise mechanism is unknown.


Cefiderocol

Cefiderocol is a cephalosporin antibacterial with activity against Gram-negative aerobic bacteria. Cefiderocol functions as a siderophore and binds to extracellular free ferric iron. In addition to passive diffusion via porin channels, cefiderocol is actively transported across the outer cell membrane of bacteria into the periplasmic space using a siderophore iron uptake mechanism. Cefiderocol exerts bactericidal action by inhibiting cell wall biosynthesis through binding to penicillin-binding proteins (PBPs)

A fourth-generation siderophore cephalosporin antibiotic having {1-[2-(2-chloro-3,4-dihydroxybenzamido)ethyl]pyrrolidinium-1-yl}methyl and [(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-{[(2-carboxypropan-2-yl)oxy]imino}acetyl]amino side groups located at positions 3 and 7 respectively, developed to combat a variety of bacterial pathogens, including beta-lactam- and carbapenem-resistant organisms.


Zanubrutinib

BRUKINSA (zanubrutinib) is a Bruton’s tyrosine kinase (BTK) inhibitor. Zanubrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. In nonclinical studies, zanubrutinib inhibited malignant B-cell proliferation and reduced tumor growth.


Cenobamate

The precise mechanism by which cenobamate exerts its therapeutic effects in patients with partial-onset seizures is unknown. Cenobamate has been demonstrated to reduce repetitive neuronal firing by inhibiting voltage-gated sodium  currents. It is also a positive allosteric modulator of the gamma-aminobutyric acid (GABAA) ion channel.


Voxelotor

Voxelotor is a hemoglobin S (HbS) polymerization inhibitor that binds to HbS with a 1:1 stoichiometry and exhibits preferential partitioning to red blood cells (RBCs). By increasing the affinity of Hb for oxygen, voxelotor demonstrates dose-dependent inhibition of HbS polymerization. Nonclinical studies suggest that voxelotor may inhibit RBC sickling, improve RBC deformability, and reduce whole blood viscosity.


GOLODIRSEN

Golodirsen is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass. It is designed to bind to exon 53 of dystrophin pre-mRNA resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Exon 53 skipping is intended to allow for production of an internally truncated dystrophin protein in patients with genetic mutations that are amenable to exon 53 skipping.


Lumateperone

The mechanism of action of lumateperone in the treatment of schizophrenia is unknown. However, the efficacy of lumateperone could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.


Lemborexant

The mechanism of action of lemborexant in the treatment of insomnia is presumed to be through antagonism of orexin receptors. The orexin neuropeptide signaling system plays a role in wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive.


Ubrogepant

Ubrogepant is a calcitonin gene-related peptide receptor antagonist.


ROMOSOZUMAB

Romosozumab-aqqg is a humanized monoclonal antibody (IgG2) produced in a mammalian cell line (Chinese Hamster Ovary) by recombinant DNA technology that binds to and inhibits the action of sclerostin, a regulatory factor in bone metabolism. Romosozumab increases bone formation and, to a lesser extent, decreases bone resorption. Animal studies showed that romosozumab-aqqg stimulates new bone formation on trabecular and cortical bone surfaces by stimulating osteoblastic activity resulting in increases in trabecular and cortical bone mass and improvements in bone structure and strength.


BROLUCIZUMAB

Brolucizumab-dbll is a humanized monoclonal single-chain Fv (scFv) antibody fragmentand a human VEGF inhibitor. Brolucizumab binds to the three major isoforms of VEGF-A (e.g., VEGF110, VEGF121, and VEGF165), thereby preventing interaction with receptors VEGFR-1 and VEGFR-2. By inhibiting VEGF-A, brolucizumab suppresses endothelial cell proliferation, neovascularization, and vascular permeability.


LUSPATERCEPT

Luspatercept-aamt is a receptor fusion protein consisting of a modified extracellular domain of the human activin receptor type IIB linked to a human IgG1 Fc domain with a calculated molecular mass of approximately 76 kD. Luspatercept is produced in Chinese hamster ovary cells by recombinant DNA technology. It binds several endogenous TGF-beta superfamily ligands, thereby diminishing Smad2/3 signaling. Luspatercept-aamt promoted erythroid maturation through differentiation of late-stage erythroid precursors (normoblasts) in mice. In a model of beta-thalassemia, luspatercept-aamt decreased abnormally elevated Smad2/3 signaling and improved hematology parameters associated with ineffective erythropoiesis in mice.


CRIZANLIZUMAB

Crizanlizumab-tmca is a humanized IgG2 kappa monoclonal antibody that binds to P-selectin and blocks interactions with its ligands including P-selectin glycoprotein ligand 1. Binding P-selectin on the surface of the activated endothelium and platelets blocks interactions between endothelial cells, platelets, red blood cells, and leukocytes.


Vaso-occlusive pain episode in sickle cell disease


BOTULINUM TOXIN TYPE A

Botulinum toxin type A (Clostridium botulinum neurotoxin) blocks peripheral acetylcholine release at presynaptic cholinergic nerve terminals by cleaving SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within the nerve endings, thereby leading to denervation of the muscle and a flaccid paralysis.


Lascufloxacin

Lascufloxacin has strong antibacterial activity against the primary causative bacteria of community-acquired respiratory infections and also exhibits good activity against streptococci and anaerobic bacteria in the oral cavity, which have attracted attention recently as the causative bacterial of community-acquired pneumonia. Meanwhile, its penetration to the tissue of the lungs, ear, nose and throatis is good, and even at small doses, it maintains an effective drug concentration in infected tissue and demonstrates a high level of therapeutic effectiveness.


Roxadustat

Roxadustat is a first-in-class orally administered inhibitor of hypoxia-inducible factor (HIF) prolylhydroxylase that corrects anemia by activating a response that occurs naturally when the body responds to reduced oxygen levels in the blood. The response activated by roxadustat involves the regulation of multiple, complementary processes to promote erythropoiesis and increase the blood’s oxygen-carrying capacity.

An N-acylglycine resulting from the formal condensation of the amino group of glycine with the carboxy group of 4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxylic acid. It is an inhibitor of hypoxia inducible factor prolyl hydroxylase (HIF-PH).


Malignant neoplasm of colon and/or rectum


retinopathy of prematurity

A bilateral retinopathy characterized by neovascularization, scarring, retinal detachment, and eventually blindness. It may be mild or severe. It occurs in babies born prematurely. Causes include oxygen toxicity and hypoxia.


Elexacaftor

Elexacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of F508del-CFTR to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect of elexacaftor, tezacaftor and ivacaftor is increased quantity and function of F508del-CFTR at the cell surface, resulting in increased CFTR activity as measured by CFTR mediated chloride transport.


AIR POLYMER-TYPE A

ExEm Foam (air polymer-type A) intrauterine foam is formed by mixing the clear Gel [polymer-type A (hydoxyethyl cellulose), glycerin, and purified water] with air and Sterile Purified Water, creating an echogenic contrast agent. When visualized with ultrasound, the foam appears echogenic or bright within the fallopian tubes and peritoneal cavity.


Givosiran is a double-stranded small interfering RNA that causes degradation of aminolevulinate synthase1 (ALAS1) mRNA in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA. This leads to reduced circulating levels of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of AHP.


Coomassie Blue G 250

Brilliant Blue G has been shown to selectively stain the ILM, but not the epiretinal membrane nor the retina, making it easier to visualize the membrane for removal, although the exact mechanism of this selectivity has not been elucidated.


Treosulfan

immunosuppressant; RN given refers to (S-(R*,R*))-isomer


Allogeneic peripheral blood stem cell transplant


ENFORTUMAB VEDOTIN

Enfortumab vedotin-ejfv is an ADC. The antibody is a human IgG1 directed against Nectin-4, an adhesion protein located on the surface of cells. The small molecule, MMAE, is a microtubule-disrupting agent, attached to the antibody via a protease-cleavable linker. Nonclinical data suggest that the anticancer activity of enfortumab vedotin-ejfv is due to the binding of the ADC to Nectin-4-expressing cells, followed by internalization of the ADC-Nectin-4 complex, and the release of MMAE via proteolytic cleavage. Release of MMAE disrupts the microtubule network within the cell, subsequently inducing cell cycle arrest and apoptotic cell death.


Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody-drug conjugate. The antibody is a humanized anti-HER2 IgG1. The small molecule, DXd, is a topoisomerase I inhibitor attached to the antibody by a cleavable linker. Following binding to HER2 on tumor cells, fam-trastuzumab deruxtecan-nxki undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon release, the membrane-permeable DXd causes DNA damage and apoptotic cell death.


Metastatic human epidermal growth factor 2 positive carcinoma of breast


Bronchopneumonia due to Haemophilus influenzae


Extensive stage primary small cell carcinoma of lung


TUROCTOCOG ALFA PEGOL

Turoctocog alfa pegol is a purified recombinant human factor VIII (rFVIII) product with a 40 kDa polyethylene-glycol (PEG) conjugated to the protein. The PEG is attached to the O-linked glycan in the truncated B-domain of rFVIII (turoctocog alfa). The mechanism of action of turoctocog alfa pegolis based on the replacement of the deficient or absent factor VIII in patients with haemophilia A.When turoctocog alfa pegol is activated by thrombin at the site of injury, the B-domain containing the PEG moiety and the a3-region are cleaved off, thus generating activated recombinant factor VIII (rFVIIIa) which is similar in structure to native factor VIIIa.


DARBEPOETIN ALFA

acts exactly like the natural erythropoietin made by the body to stimulate red blood cell production, but it is very slightly different in its structure


Anemia due to and following chemotherapy


Legionnaires' disease

A pneumonia caused by Legionella pneumophila and other Legionella species, which is characterized by fever, cough, progressive respiratory distress, and which is often accompanied by extrapulmonary manifestations.


Pneumonia caused by Chlamydia pneumoniae


Relebactam

RECARBRIO is a combination of imipenem/cilastatin and relebactam. Imipenem is a penem antibacterial drug, cilastatin sodium is a renal dehydropeptidase inhibitor, and relebactam is a beta lactamase inhibitor. Cilastatin limits the renal metabolism of imipenem and does not have antibacterial activity. The bactericidal activity of imipenem results from binding to PBP 2 and PBP 1B in Enterobacteriaceae and Pseudomonas aeruginosa and the subsequent inhibition of penicillin binding proteins (PBPs). Inhibition of PBPs leads to the disruption of bacterial cell wall synthesis. Imipenem is stable in the presence of some beta lactamases. Relebactam  has  no  intrinsic  antibacterial  activity. Relebactam protects  imipenem  from  degradation  by certain serine beta lactamases such as Sulhydryl Variable (SHV), Temoneira (TEM), Cefotaximase-Munich 13 Reference ID: 4462927 (CTX-M), Enterobacter   cloacae P99   (P99), Pseudomonas-derived   cephalosporinase   (PDC),   and Klebsiella-pneumoniae carbapenemase (KPC)


Gastrointestinal infection caused by Klebsiella aerogenes


Pseudomonas gastrointestinal tract infection


Solid neoplasm with neurotrophic receptor tyrosine kinase gene fusion


Influenza caused by pandemic influenza virus


myelodysplastic syndrome with single lineage dysplasia

A myelodysplastic syndrome characterized by dysplasia seen in at least 10% of the early cells of 1 cell type (either red blood cells, white blood cells, or megakaryocytes) in the bone marrow.


Avapritinib

Avapritinib is a tyrosine kinase inhibitor that targets PDGFRA and PDGFRA D842 mutants as well as multiple KIT exon 11, 11/17 and 17 mutants with half maximal inhibitory concentrations (IC50s) less than 25 nM. Certain mutations in PDGFRA and KIT can result in the autophosphorylation and constitutive activation of these receptors which can contribute to tumor cell proliferation. Other potential targets for avapritinib include wild type KIT, PDGFRB, and CSFR1.


Tazemetostat

Tazemetostat is an inhibitor of the methyltransferase, EZH2, and some EZH2 gain-of-function mutations including Y646X and A687V. Tazemetostat also inhibited EZH1 with a half-maximal inhibitory concentration (IC50) of 392 nM, approximately 36 times higher than the IC50 for inhibition of EZH2


epithelioid sarcoma

An aggressive malignant neoplasm of uncertain differentiation, characterized by the presence of epithelioid cells forming nodular patterns. The nodules often undergo central necrosis, resulting in a pseudogranulomatous growth pattern. It usually occurs in young adults. The most common sites of involvement are the extremities (distal-type epithelioid sarcoma), and less frequently the pelvis, perineum, and genital organs (proximal-type epithelioid sarcoma).


Rimegepant

Rimegepant is a calcitonin gene-related peptide receptor antagonist


Bempedoic acid

Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) by inhibition of cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Bempedoic acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively. ACSVL1 is expressed primarily in the liver. Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein receptors

An alpha,omega-dicarboxylic acid that is pentadecanedioic acid which is substituted by methyl groups groups at positions 2 and 14, and by a hydroxy group at position 8. It is a drug used for the treatment of high LDL cholesterol, which is sometimes referred to as 'bad cholesterol'.


Lactitol

A glycosyl alditol consisting of beta-D-galactopyranose and D-glucitol joined by a 1->4 glycosidic bond. It is used as a laxative, as an excipient, and as replacement bulk sweetener in some low-calorie foods.


Ozanimod

Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Ozanimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which ozanimod exerts therapeutic effects in multiple sclerosis is unknown but may involve the reduction of lymphocyte migration into the central nervous system


intermediate coronary syndrome

Angina pectoris (or equivalent type of ischemic discomfort) which has recently changed in frequency, duration, intensity, or occurs at rest.


Mobitz type II atrioventricular block

A disorder characterized by an electrocardiographic finding of intermittent failure of atrial electrical impulse conduction to the ventricles, characterized by a relatively constant PR interval prior to the block of an atrial impulse. (CDISC)


sinoatrial block

A heart block that is initiated in the sinoatrial node.


Osilodrostat

Osilodrostat is a cortisol synthesis inhibitor. It inhibits 11beta-hydroxylase (CYP11B1), the enzyme responsible for the final step of cortisol biosynthesis in the adrenal gland


Cushing disease due to pituitary adenoma

Cushing's syndrome due to abnormally high secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland.


ISATUXIMAB

Isatuximab-irfc is an IgG1-derived monoclonal antibody that binds to CD38 expressed on the surface of hematopoietic and tumor cells, including multiple myeloma cells. Isatuximab-irfc induces apoptosis of tumor cells and activation of immune effector mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement dependent cytotoxicity (CDC). Isatuximab-irfc inhibits the ADP-ribosyl cyclase activity of CD38. Isatuximab-irfc can activate natural killer (NK) cells in the absence of CD38-positive target tumor cells and suppresses CD38-positive T-regulatory cells. The combination of isatuximab-irfc and pomalidomide enhanced ADCC activity and direct tumor cell killing compared to that of isatuximab-irfc alone in vitro, and enhanced antitumor activity compared to the activity of isatuximab-irfc or pomalidomide alone in a human multiple myeloma xenograft model


EPTINEZUMAB

Eptinezumab-jjmr is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor


Onilcamotide

Teprotumumab-trbw’s mechanism of action in patients with Thyroid Eye Disease has not been fully characterized. Teprotumumab-trbw binds to IGF-1R and blocks its activation and signaling


endocrine exophthalmos

Progressive inflammation and damage to tissues around the eyes, especially extraocular muscle, connective, and fatty tissue occurring in patients with hyperthyroidism or a history of hyperthyroidism due to Graves’ disease.


Oxybuprocaine

A benzoate ester in which 4-amino-3-butoxybenzoic acid and 2-(diethylamino)ethanol have combined to form the ester bond; an ester-based local anaesthetic (ester "caine") used especially in ophthalmology and otolaryngology.


Topical local anesthetic to eye (procedure)


Fluorescein

A phthalic indicator dye that appears yellow-green in normal tear film and bright green in a more alkaline medium such as the aqueous humor.

A xanthene dye that is highly fluorescent, detectable even when present in minute quantities. Used forensically to detect traces of blood, in analytical chemistry as an indicator in silver nitrate titrations and in microscopy.


Selumetinib

Selumetinib is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2). MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. Both MEK and ERK are critical components of the RAS-regulated RAF-MEK-ERK pathway, which is often activated in different types of cancers

A member of the class of benzimidazoles that is 1-methyl-1H-benzimidazole which is substituted at positions 4, 5, and 6 by fluorine, (4-bromo-2-chlorophenyl)amino, and N-(2-hydroxyethoxy)aminocarbonyl groups, respectively. It is a MEK1 and MEK2 inhibitor.


neurofibromatosis type 1

A clinically heterogeneous, neurocutaneous genetic disorder characterized by cafe-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, and multiple neurofibromas.


Pemigatinib

Pemigatinib inhibited FGFR1-3 phosphorylation and signaling and decreased cell viability in cancer cell lines with activating FGFR amplifications and fusions that resulted in constitutive activation of FGFR signaling.


Tucatinib

Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and showed anti-tumor activity in HER2 expressing tumor cells. In vivo, tucatinib inhibited the growth of HER2 expressing tumors. The combination of tucatinib and trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either drug alone


SATRALIZUMAB

Satralizumab-mwge is a recombinant humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody based on a human IgG2 framework. It is an interleukin-6 (IL-6) receptor antagonist indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients. The precise mechanism by which satralizumab-mwge exerts therapeutic effects in NMOSD is unknown but is presumed to involve inhibition of IL-6-mediated signaling through binding to soluble and membrane-bound IL-6 receptors.


Cortexolone 17alpha-propionate

Clascoterone is an androgen receptor inhibitor. The mechanism of action of Winlevi cream for the topical treatment of acne vulgaris is unknown.


Copper dotatate Cu-64

Copper Cu-64 dotatate is a radioactive diagnostic drug. It binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSTR2). It binds to cells that express somatostatin receptors including malignant neuroendocrine cells, which overexpress SSTR2 receptors. Copper Cu 64 is a positron (beta+) emitting radionuclide with an emission yield that allows positron emission tomography (PET) imaging.


Pralsetinib

Pralsetinib is a kinase inhibitor of wild-type RET and oncogenic RET fusions (CCDC6-RET) and mutations (RET V804L, RET V804M and RET M918T) with half maximal inhibitory concentrations (IC50s) less than 0.5 nM. In purified enzyme assays, pralsetinib inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRb, and FGFR1 at higher concentrations that were still clinically achievable at Cmax. In cellular assays, pralsetinib inhibited RET at approximately 14-, 40-, and 12-fold lower concentrations than VEGFR2, FGFR2, and JAK2, respectively.


BAMLANIVIMAB

Effective April 16, 2021, FDA revoked the EUA for use of bamlanivimab alone (monotherapy) for the treatment of mild to moderate COVID-19. The EUA for use of bamlanivimab in a combined regimen with etesevimab remains unchanged. Bamlanivimab is a recombinant neutralizing human IgG1kappa monoclonal antibody (mAb) to the spike protein of SARS-CoV-2, and is unmodified in the Fc region. Bamlanivimab binds to spike protein and blocks spike protein attachment to the human ACE2 receptor with an IC50 value of 0.025 μg/mL.


A disease caused by infection with severe acute respiratory syndrome coronavirus 2.


Somapacitan beco

Somapacitan-beco is a human growth hormone (hGH) analog. It binds to a dimeric GH receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects. Some of these pharmacodynamic effects are primarily mediated by insulin-like growth factor I (IGF-I) produced in the liver, while others are primarily a consequence of the direct effects of somapacitan-beco.


Lonafarnib

Lonafarnib inhibits farnesyltransferase to prevent farnesylation and subsequent accumulation of progerin and progerin-like proteins in the inner nuclear membrane.

A 4-{2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl]-2-oxoethyl}piperidine-1-carboxamide that has R configuration. It is used as oral farnesyltransferase inhibitor.


Hutchinson-Gilford progeria syndrome

Hutchinson-Gilford progeria syndrome is a rare, fatal, autosomal dominant and premature aging disease, beginning in childhood and characterized by growth reduction, failure to thrive, a typical facial appearance (prominent forehead, protuberant eyes, thin nose with a beaked tip, thin lips, micrognathia and protruding ears) and distinct dermatologic features (generalized alopecia, aged-looking skin, sclerotic and dimpled skin over the abdomen and extremities, prominent cutaneous vasculature, dyspigmentation, nail hypoplasia and loss of subcutaneous fat).


Setmelanotide

Setmelanotide is an 8 amino acid cyclic peptide analog of endogenous melanocortin peptide alpha-MSH (alpha-melanocyte stimulating hormone). It is a melanocortin 4 (MC4) receptor agonist, with 20-fold less activity at the melanocortin 3 (MC3) and melanocortin 1 (MC1) receptors.


BULEVIRTIDE

Bulevirtide is an antiviral medicine used to treat chronic (long-term) hepatitis delta virus (HDV) infection in adults with compensated liver disease (when the liver is damaged but is still able to work), when the presence of viral RNA (genetic material) has been confirmed by blood tests. Bulevirtide blocks the entry of HBV and HDV into hepatocytes by binding to and inactivating NTCP, a bile salt liver transporter serving as essential HBV/HDV entry receptor.


Chronic viral hepatitis B with hepatitis D


IMLIFIDASE

Imlifidase is a cysteine protease derived from the immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that cleaves the heavy chains of all human IgG subclasses but no other immunoglobulins. The cleavage of IgG leads to elimination of Fc-dependent effector functions, including CDC and antibody-  dependent cell-mediated cytotoxicity (ADCC). By cleaving all IgG, imlifidase reduces the level of DSA, thus enabling transplantation.


gram-negative bacterial infections

Infections caused by bacteria that show up as pink (negative) when treated by the gram-staining method.


Filgotinib

Filgotinib is an adenosine triphosphate (ATP)-competitive and reversible inhibitor of the JAK family. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane. JAK1 is important in mediating inflammatory cytokine signals, JAK2 in mediating myelopoiesis and erythropoiesis and JAK3 plays critical roles in immune homeostasis and lymphopoiesis. Within the signalling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs) which modulate intracellular activity including gene expression. Filgotinib modulates these signalling pathways by preventing the phosphorylation and activation of STATs.


Vadadustat

Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor induces endogenous erythropoietin synthesis and enhances iron mobilization.


Daprodustat

Daprodustat is a small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (PHD) developed for the treatment of anaemia in patients with chronic kidney disease (CKD). Inhibition of PHD prevents degradation of hypoxia-inducible factor (HIF), leading to the production of erythropoietin and subsequent induction of erythropoiesis.


BORONOPHENYLALANINE, DL-

Borofalan is a boron compound, namely phenylalanine labeled with 10B (an isotope of boron). Phenylalanine is an amino acid essential for the growth of tumor cells. It has been suggested that the compound accumulatesin tumor cells, mediated by L-type amino acid transporter-1 (LAT-1), an amino acid transporter highly expressed in multiple types of carcinomas including head and neck cancer. Borofalan alone does not inhibit tumor growth, whereas upon irradiation of neutron beams from outside the body, 10B atoms incorporated in tumorcells capture neutrons, resulting in the release of alpha rays and lithium nuclei generated by nuclear reaction, exhibiting a tumor growth-inhibitory effect.


Tirabrutinib

Tirabrutinib is a potent and selective Bruton’s tyrosine kinase (BTK) inhibitor that irreversibly and covalently binds to BTK Cys-481 in B cells and inhibits aberrant B cell receptor signalling in B cell-related cancers and autoimmune diseases.


primary central nervous system lymphoma

A non-Hodgkin or Hodgkin lymphoma that arises in the brain or spinal cord as a primary lesion. There is no evidence of lymphoma outside the central nervous system at the time of diagnosis.


Dotinurad

Dotinurad, a novel selective urate reabsorption inhibitor, reduces serum uric acid levels by selectively inhibiting urate transporter 1 (URAT1), which is expressed on the proximal renal tubules and is responsible for reabsorption of uric acid.


enarodustat

Enarodustat is an orally active inhibitor of hypoxia inducible factor-proly hydroxylase (HIF-PH) being developed for the treatment of anaemia associated with chronic kidney disease (CKD).


Tepotinib

Tepotinib is a MET (mesenchymal-epithelial transition factor) tyrosine kinase inhibitor being developed for the treatment of solid tumours. It selectively binds to MET and inhibits MET phosphorylation disrupting the oncogenic MET receptor signalling caused by MET gene alterations, including both MET exon 14 (METex14) skipping alterations and MET protein overexpression. This results in cell death in tumour cells overexpressing MET protein or expressing constitutively activated MET protein.


Delgocitinib

Delgocitinib, a janus kinase (JAK) inhibitor, is being approved for the treatment of inflammatory skin conditions. Delgocitinib inhibited the activation of inflammatory cells, such as T cells, B cells, monocytes and mast cells, in vitro and inhibited Th1-, Th2- and Th17-type cytokine production from both T cells and non-T cells.

A pyrrolopyrimidine that is 7H-pyrrolo[2,3-d]pyrimidine substituted by a (3S,4R)-1-(cyanoacetyl)-3-methyl-1,6-diazaspiro[3.4]octan-6-yl group at position 4. It is a pan-Janus kinase (JAK) inhibitor and is approved for treatment of atopic dermatitis (AD) in Japan.


Sofpironium

Sofpironium bromide gel is a topical anticholinergic agent developed for the treatment of hyperhidrosis. The drug is designed to reduce sweating by inhibiting M3 muscarinic receptors in eccrine glands at the application site.


Psma-hbed-cc ga-68

Ga-68 PSMA-11 is a radioactive diagnostic agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer. Ga-68 PSMA-11 binds to cells that express PSMA, including malignant prostate cancer cells, which usually overexpress PSMA.


Orladeyo

Berotralstat is a plasma kallikrein inhibitor that binds to plasma kallikrein and inhibits its proteolytic activity. Plasma kallikrein is a protease that cleaves high-molecular-weight-kininogen (HMWK) to generate cleaved HMWK (cHMWK) and bradykinin, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE. In patients with HAE due to C1-inhibitor (C1-INH) deficiency or dysfunction, normal regulation of plasma kallikrein activity is not present, which leads to uncontrolled increases in plasma kallikrein activity and results in angioedema attacks. Berotralstat decreases plasma kallikrein activity to control excess bradykinin generation in patients with HAE.


Tirbanibulin is a microtubule inhibitor developed for the topical treatment of actinic keratosis. The mechanism of action is not fully understood. However, it is known that tirbanibulin inhibits proliferation of keratinocytes through inhibition of tubulin polymerization and disruption of Src tyrosine kinase signaling. This results in disruption of the intracellular microtubule network, resulting in cell cycle arrest and apoptosis of keratinocytes.


ANSUVIMAB

EBANGA (ansuvimab-zykl) is a Zaire ebolavirus (EBOV) glycoprotein 1 (GP1)-directed recombinant, human IgG1kappa monoclonal antibody that binds to the glycan cap and inner chalice of the EBOV GP1 subunit. The epitope to which it binds is located within the receptor binding domain of EBOV consisting of amino acids LEIKKPDGS (GP residues 111–119).


Ebola hemorrhagic fever

A viral hemorrhagic fever that is caused by the Ebola virus, which is transmitted by contact with infected animals or humans; it is characterized by high fever, unexplained bleeding, and a high mortality rate.


MARGETUXIMAB

Margetuximab-cmkb, a HER2/neu receptor antagonist, is a chimeric Fc-engineered IgG1 kappa monoclonal antibody. It binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER2). Upon binding to HER2-expressing tumor cells, margetuximab-cmkb inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain and mediates antibody-dependent cellular cytotoxicity (ADCC).


NAXITAMAB

Naxitamab-gqgk is a glycolipid disialoganglioside (GD2)-binding recombinant humanized monoclonal IgG1 antibody, that contains human framework regions and murine complementarity-determining regions. Naxitamab-gqgk binds to the glycolipid GD2. GD2 is a disialoganglioside that is overexpressed on neuroblastoma cells and other cells of neuroectodermal origin, including the central nervous system and peripheral nerves. In vitro, naxitamab-gqgk was able to bind to cell surface GD2 and induce complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC).


ATOLTIVIMAB

Atoltivimab in combination with odesivimab and maftivimab has been approved as INMAZEB for the treatment of infection caused by Zaire ebolavirus. INMAZEB is a combination of the three recombinant human IgG1kappa monoclonal antibodies that inhibit Zaire ebolavirus, each targeting the Zaire ebolavirus glycoprotein (GP). Maftivimab is a neutralizing antibody that blocks entry of the virus into susceptible cells. Odesivimab is a non-neutralizing antibody that induces antibody-dependent effector function through FcyRIIIa signaling when bound to its target. Odesivimab also binds to the soluble form of Zaire ebolavirus glycoprotein (sGP). Atoltivimab combines both neutralization and FcgammaRIIIa signaling activities.


MAFTIVIMAB

Maftivimab in combination with odesivimab and atoltivimab has been approved as INMAZEB for the treatment of infection caused by Zaire ebolavirus. INMAZEB is a combination of the three recombinant human IgG1kappa monoclonal antibodies that inhibit Zaire ebolavirus, each targeting the Zaire ebolavirus glycoprotein (GP). Maftivimab is a neutralizing antibody that blocks entry of the virus into susceptible cells. Odesivimab is a non-neutralizing antibody that induces antibody-dependent effector function through FcyRIIIa signaling when bound to its target. Odesivimab also binds to the soluble form of Zaire ebolavirus glycoprotein (sGP). Atoltivimab combines both neutralization and FcgammaRIIIa signaling activities.


ODESIVIMAB

Odesivimab in combination with maftivimab and atoltivimab has been approved as INMAZEB for the treatment of infection caused by Zaire ebolavirus. INMAZEB is a combination of the three recombinant human IgG1kappa monoclonal antibodies that inhibit Zaire ebolavirus, each targeting the Zaire ebolavirus glycoprotein (GP). Maftivimab is a neutralizing antibody that blocks entry of the virus into susceptible cells. Odesivimab is a non-neutralizing antibody that induces antibody-dependent effector function through FcgammaRIIIa signaling when bound to its target. Odesivimab also binds to the soluble form of Zaire ebolavirus glycoprotein (sGP). Atoltivimab combines both neutralization and FcgammaRIIIa signaling activities.


hypersomnia

A sleep disorder characterized by excessive sleepiness.


neovascular glaucoma

Neovascular glaucoma is the most common type of secondary glaucoma, usually caused by diabetic retinopathy, central retinal vein occlusion and carotid artery obstruction but sometimes by trauma, uvietis or ocular tumors, and characterized by severe eye pain, synechial angle glaucoma, high intraocular pressure and leading to loss of vision.


chronic rhinosinusitis

Chronic form of sinusitis.


marginal zone lymphoma

A usually indolent mature B-cell lymphoma, arising from the marginal zone of lymphoid tissues. It is characterized by the presence of small to medium sized atypical lymphocytes. It comprises three entities, according to the anatomic sites involved: extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, which affects extranodal sites (most often stomach, lung, skin, and ocular adnexa); nodal marginal zone B-cell lymphoma, which affects lymph nodes without evidence of extranodal disease; and splenic marginal zone B-cell lymphoma, which affects the spleen and splenic hilar lymph nodes, bone marrow, and often the peripheral blood.


Anaplastic lymphoma kinase positive anaplastic large cell lymphoma


metastatic prostate carcinoma

A carcinoma that arises from the prostate gland and has spread to other anatomic sites.


familial hyperinsulinism

An instance of hyperinsulinism (disease) that is caused by an inherited modification of the individual's genome.


metastasis from malignant neoplasm of thyroid


Triheptanoin

Triheptanoin is a medium-chain triglyceride consisting of three odd-chain 7-carbon length fatty acids (heptanoate) that provide a source of calories and fatty acids to bypass the long-chain FAOD enzyme deficiencies for energy production and replacement


inherited fatty acid metabolism disorder

A group of genetic disorders that result from the inability to produce or use an enzyme required to oxidize fatty acids, resulting in an inability to generate energy from fatty acid sources.


Long-chain fatty acid transport deficiency


Fostemsavir

Fostemsavir is a prodrug without significant biochemical or antiviral activity that is hydrolyzed to the active moiety, temsavir, which is an HIV-1 attachment inhibitor. Temsavir binds directly to the gp120 subunit within the HIV-1 envelope glycoprotein gp160 and selectively inhibits the interaction between the virus and cellular CD4 receptors, thereby preventing attachment. Additionally, temsavir can inhibit gp120-dependent post-attachment steps required for viral entry into host cells.


Human immunodeficiency virus I infection


Drug induction of cytochrome p450 CYP3A enzyme


cancer

A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas (adenocarcinomas or squamous cell carcinomas), Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.


Drug inhibition of cytochrome p450 CYP3A enzyme


LUMASIRAN

Lumasiran is a hydroxyacid oxidase 1 (HAO1)-directed double-stranded small interfering ribonucleic acid (siRNA), covalently linked to a ligand containing N-acetylgalactosamine (GalNAc). It reduces levels of glycolate oxidase (GO) enzyme by targeting the HAO1 gene messenger ribonucleic acid (mRNA) in hepatocytes through RNA interference. Decreased GO enzyme levels reduce the amount of available glyoxylate, a substrate for oxalate production. As the GO enzyme is upstream of the deficient alanine:glyoxylate aminotransferase (AGT) enzyme that causes PH1, the mechanism of action of lumasiran is independent of the underlying AGXT gene mutation.


primary hyperoxaluria type 1

A rare disorder of glyoxylate metabolism characterized by the accumulation of oxalate due to a deficiency of the peroxisomal hepatic enzyme L-alanine: glyoxylate aminotransferase (AGT). Clinical presentation is variable, ranging from occasional symptomatic nephrolithiasis to nephrocalcinosis and end-stage renal disease with systemic involvement.


Relugolix

Relugolix is a nonpeptide GnRH receptor antagonist that competitively binds to pituitary GnRH receptors, thereby, reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and consequently testosterone.


Lower Abdominal Pain

A sensation of discomfort emanating from the inferior quadrants of the abdomen, which may be peritoneal or visceral in origin, or referred from an extra-abdominal location.


Abnormal uterine bleeding due to uterine fibroid


Aminopterin

Aminopterin is a folic acid amino derivative with antineoplastic and immunosuppressive properties. It binds competitively to the folate binding site of the enzyme dihydrofolate reductase, blocking tetrahydrofolate synthesis, and resulting in depletion of nucleotide precursors and inhibition of DNA, RNA and protein synthesis.


Acetylcholine

A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Miochol-E (acetylcholine chloride intraocular solution) is used to obtain miosis of the iris in seconds after delivery of the lens in cataract surgery, in penetrating keratoplasty, iridectomy and other anterior segment surgery where rapid miosis may be required.

Actylcholine is an ester of acetic acid and choline, which acts as a neurotransmitter.


Aclarubicin

An anthracycline produced by Streptomyces galilaeus. It has potent antineoplastic activity.Aclarubicin is evaluated for the treatment of different conditions like acute myeloid leukemia, thyroid cancer, gastric cancer, lymphoma, small cell lung cancer. It is an inhibitor of topoisomerase II inhibitor being used in combination with different anticancerous drugs to obtain best therapeutic results and to reduce toxicity or side effects.

An anthracycline antibiotic that is produced by Streptomyces galilaeus and also has potent antineoplastic activity.


An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.

An adenosine 5'-phosphate in which the 5'-phosphate is a triphosphate group. It is involved in the transportation of chemical energy during metabolic pathways.


Adinazolam

A triazolo[4,3-a][1,4]benzodiazepine having a dimethylaminomethyl group at the 1-position, a phenyl group at the 6-position and a chloro substituent at the 8-position.


Ajmaline

An alkaloid found in the root of RAUWOLFIA SERPENTINA, among other plant sources. It is a class Ia antiarrhythmic agent that apparently acts by changing the shape and threshold of cardiac action potentials.


Alacepril

It is an angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. It used for the treatment of essential or renovascular hypertension (usually administered with other drugs, particularly thiazide diuretics).


Alizapride

a dopamine antagonist with prokinetic and antiemetic effects used in the treatment of nausea and vomiting, including postoperative nausea and vomiting. Its effect is due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone (CTZ) in the central nervous system (CNS), this action prevents nausea and vomiting triggered by most stimuli.


Alpidem

Alpidem shows anxiolytic and anticonvulsant properties which appear to be elicited both with a direct mechanism through the interaction with central benzodiazepine receptor (CBR) and with an indirect mechanism by the interaction with peripheral benzodiazepine receptor (PBR) as well as the stimulation of pregnenolone formation. Alpidem was briefly marketed for the treatment of anxiety, but was withdrawn because of liver toxicity.


Vericiguat

Vericiguat is a stimulator of soluble guanylate cyclase (sGC), an important enzyme in the nitric oxide (NO) signaling pathway. When NO binds to sGC, the enzyme catalyzes the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger that plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. Heart failure is associated with impaired synthesis of NO and decreased activity of sGC, which may contribute to myocardial and vascular dysfunction. By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation.

A pyrazolopyridine that is 5-fluoro-1H-pyrazolo[3,4-b]pyridine in which the amino hydrogen at position 1 has been substituted by a 2-fluorobenzyl group and the hydrogen at position 3 has been substituted by a 4,6-diamino-5-[(methoxycarbonyl)amino]pyrimidin-2-yl group. It is a soluble guanylate cyclase stimulator which is used for treatment of chronic heart failure.


Voclosporin

Voclosporin is a calcineurin-inhibitor immunosuppressant. The mechanism of voclosporin suppression of calcineurin has not been fully established. Activation of lymphocytes involves an increase in intracellular calcium concentrations that bind to the calcineurin regulatory site and activate calmodulin binding catalytic subunit and through dephosphorylation activates the transcription factor, Nuclear Factor of Activated T-Cell Cytoplasmic (NFATc). The immunosuppressant activity results in inhibition of lymphocyte proliferation, T-cell cytokine production, and expression of T-cell activation surface antigens.


lupus nephritis

Glomerulonephritis in the context of systemic lupus erythematosus.


Umbralisib

Umbralisib inhibits multiple kinases. In biochemical and cell-based assays, umbralisib inhibited PI3Kdelta and casein kinase CK1-epsilon. PI3K-delta is expressed in normal and malignant B-cells; CK1-epsilon has been  implicated in the pathogenesis of cancer cells, including lymphoid malignancies. Umbralisib also inhibited a mutated form of ABL1 in biochemical assays. Umbralisib inhibited cell proliferation, CXCL12-mediated cell adhesion, and CCL19-mediated cell migration in lymphoma cell lines in studies conducted in vitro.


CASIMERSEN

Casimersen is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass. Casimersen is designed to bind to exon 45 of dystrophin pre-mRNA resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 45 skipping. Exon 45 skipping is intended to allow for production of an internally truncated dystrophin protein in patients with genetic mutations that are amenable to exon 45 skipping.


Cyclic pyranopterin monophosphate

Fosdenopterin provides an exogenous source of cPMP. cPMP is converted to molybdopterin, which is then converted to molybdenum cofactor (MoCo) and restores molybdenum cofactor biosynthesis. In MOCD Type A,  mutations in MOCS1 lead to deficient MOCS1A/B-dependent synthesis of cPMP, which subsequently results in deficient molybdenum-dependent enzyme activity (e.g., sulfite oxidase).

A linear-fused organic heterotetracyclic compound consisting of a [1,3,2]dioxaphosphinane fused to a pyran ring which is in turn fused to a pteridine ring system. Molybdenum cofactor biosynthesis intermediate. Dehydrated derivative known as precursor Z.


sulfite oxidase deficiency due to molybdenum cofactor deficiency type A

An autosomal recessive condition that is caused by mutation(s) in the MOCS1 gene, encoding molybdenum cofactor biosynthesis protein 1. it is characterized by poor feeding, encephalopathy, seizures and dysmorphic facial features.


Melphalan flufenamide

Melphalan flufenamide is a peptide conjugated alkylating drug. Due to its lipophilicity, melphalan flufenamide is passively distributed into cells and thereafter enzymatically hydrolyzed to melphalan. Similar to other nitrogen mustard drugs, crosslinking of DNA is involved in the antitumor activity of melphalan flufenamide. In cellular assays, melphalan flufenamide inhibited proliferation and induced apoptosis of hematopoietic and solid tumor cells. Additionally, melphalan flufenamide showed synergistic cytotoxicity with dexamethasone in melphalan resistant and non-resistant multiple myeloma cell lines.


Ponesimod

Ponesimod is a sphingosine 1-phosphate (S1P) receptor 1 modulator that binds with high affinity to S1P receptor 1. Ponesimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which ponesimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system


Dasiglucagon

Dasiglucagon is a glucagon receptor agonist, which increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for dasiglucagon to produce an antihypoglycemic effect.


Serdexmethylphenidate

Serdexmethylphenidate is a prodrug of dexmethylphenidate (d-MPH). The mode of therapeutic action in ADHD is not known. Serdexmethylphenidate is not deemed to have pharmacological activity until converted to d-MPH. Dexmethylphenidate HCl is a central nervous system (CNS) stimulant that blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.


EVINACUMAB

Evinacumab-dgnb is a recombinant human monoclonal antibody that binds to and inhibits ANGPTL3. ANGPTL3 is a member of the angiopoietin-like protein family that is expressed primarily in the liver and plays a role in the regulation of lipid metabolism by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL). Evinacumab-dgnb inhibition of ANGPTL3 leads to reduction in LDL-C, HDL-C, and triglycerides (TG). Evinacumab-dgnb reduces LDL-C independent of the presence of LDL receptor (LDLR) by promoting very low-density lipoprotein (VLDL) processing and clearance upstream of LDL formation. Evinacumab-dgnb blockade of ANGPTL3 lowers TG and HDL-C by rescuing LPL and EL activities, respectively.


Estetrol

Estetrol is a synthetic analogue of a native estrogen present during pregnancy, that is selective for nuclear estrogen receptors ERalpha and ERbeta. It is used in combination with drospirenone, a spironolactone analogue with anti-mineralocorticoid and antiandrogenic activity, (nextstellis) as oral contraceptive.

A 3-hydroxy steroid that is 17beta-estradiol which has been substituted at the 15alpha and 16alpha positions by two additional hydroxy groups. It is a natural estrogen produced exclusively during pregnancy by the fetal liver.


hepatocellular adenoma

A benign epithelial neoplasm arising from the hepatocytes. Grossly, it appears as a soft, round mass which often contains areas of hemorrhage and necrosis. Morphologically, the neoplastic cells resemble normal hepatocytes and form plates separated by sinusoids. Most patients have a history of contraceptive or anabolic steroids use.


DOSTARLIMAB

Dostarlimab-gxly is a humanized monoclonal antibody of the IgG4 isotype that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors.


LONCASTUXIMAB TESIRINE

Loncastuximab tesirine-lpyl is an antibody-drug conjugate (ADC) targeting CD19. The monoclonal IgG1 kappa antibody component binds to human CD19, a transmembrane protein expressed on the surface of cells of B-lineage origin. The small molecule component is SG3199, a PBD dimer and alkylating agent. Upon binding to CD19, loncastuximab tesirine-lpyl is internalized followed by release of SG3199 via proteolytic cleavage. The released SG3199 binds to the DNA minor groove and forms highly cytotoxic DNA interstrand crosslinks, subsequently inducing cell death. Loncastuximab tesirine-lpyl had anticancer activity in animal models of lymphoma.


B-cell neoplasm

A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.


Trilaciclib

Trilaciclib is a transient inhibitor of CDK 4 and 6. Hematopoietic stem and progenitor cells (HSPCs) in the bone marrow give rise to circulating neutrophils, RBCs, and platelets. HSPC proliferation is dependent on CDK4/6 activity.


Myelosuppression

A laboratory test result indicating low production of erythrocytes, leukocytes and/or thrombocytes from the bone marrow.


Cabotegravir

Cabotegravir is an HIV-1 antiretroviral drug. Cabotegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle. It is indicated in combination with rilpivirine, an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI), as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.

A monocarboxylic acid amide obtained by formal condensation of the carboxy group of (3S,11aR)-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxylic acid with the amino group of 2,4-difluorobenzylamine. Used (as its sodium salt) for treatment of HIV-1.


Post-polycythemia vera myelofibrosis

Progression of polycythemia vera characterized by decreased erythropoiesis and granulopoiesis, reticulin and collagen fibrosis of the bone marrow, leucoerythroblastic reaction in the peripheral blood, poikilocytosis, tear-drop shaped red blood cells, and splenomegaly.


Myelofibrosis that develops in a patient with history of essential thrombocythemia.


biliary tract cancer

A malignant neoplasm involving the biliary tree


FDA issued an Emergency Use Authorization (EUA) for etesevimab and bamlanivimab on February 9, 2021 that permits combined use of the drugs for the treatment of mild to moderate COVID-19. The EUA of bamlanivimab ALONE was revoked by FDA but the use of bamlanivimab in a combined regimen with etesevimab remains unchanged. Etesevimab is a recombinant neutralizing human IgG1kappa mAb to the spike protein of SARS-CoV-2, with amino acid substitutions in the Fc region (L234A, L235A) to reduce effector function. Etesevimab binds the spike protein  and blocks spike protein attachment to the human ACE2 receptor with an IC50value of 0.32 nM (0.046 μg/mL). Bamlanivimab and etesevimab bind to different but overlapping epitopes in the receptor binding domain (RBD) of the S-protein. Using both antibodies together is expected to reduce the risk of viral resistance.


CASIRIVIMAB

Casirivimab with imdevimab to be administered together is authorized for use under an EUA for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization. Casirivimab(IgG1kappa) and imdevimab (IgG1lambda) are two recombinant human mAbs which are unmodified in the Fc regions.  Casirivimab and imdevimab bind to non-overlapping epitopes of the spike protein receptor binding domain (RBD) of SARS-CoV-2. Casirivimab, imdevimab and casirivimab and imdevimab together blocked RBD binding to the human ACE2 receptor with IC50 values of 56.4 pM, 165 pM and 81.8 pM, respectively.


IMDEVIMAB

Imdevimab with casirivimab to be administered together is authorized for use under an EUA for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization. Casirivimab(IgG1kappa) and imdevimab (IgG1lambda) are two recombinant human mAbs which are unmodified in the Fc regions.  Casirivimab and imdevimab bind to non-overlapping epitopes of the spike protein receptor binding domain (RBD) of SARS-CoV-2. Casirivimab, imdevimab and casirivimab and imdevimab together blocked RBD binding to the human ACE2 receptor with IC50 values of 56.4 pM, 165 pM and 81.8 pM, respectively.


PEGCETACOPLAN

Pegcetacoplan binds to complement protein C3 and its activation fragment C3b, thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation. In PNH, extravascular hemolysis (EVH) is facilitated by C3b opsonization while intravascular hemolysis (IVH) is mediated by the downstream membrane attack complex (MAC). Pegcetacoplan acts proximally in the complement cascade controlling both C3b-mediated EVH and terminal complement-mediated IVH.


Hemophilus influenza infection

An infection that is caused by the organism Hemophilus influenza.


Dcfpyl F-18

Piflufolastat F 18 binds to cells that express PSMA (prostate-specific membrane antigen), including malignant prostate cancer cells, which usually overexpress PSMA. Fluorine-18 (F 18) is a β+ emitting radionuclide that enables positron emission tomography.


Infigratinib

Infigratinib is a small molecule kinase inhibitor of FGFR with IC50 values of 1.1, 1, 2, and 61 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively. The major human metabolites of infigratinib, BHS697 and CQM157, have similar in vitro binding affinities for FGFR1, FGFR2, and FGFR3 compared to infigratinib. Infigratinib inhibited FGFR signaling and decreased cell proliferation in cancer cell lines with activating FGFR amplifications, mutations, or fusions. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. Infigratinib had anti-tumor activity in mouse and rat xenograft models of human tumors with activating FGFR2 or FGFR3 alterations, including two patient-derived xenograft models of cholangiocarcinoma that expressed FGFR2-TTC28 or FGFR2-TRA2B fusions. Infigratinib demonstrated brain-to-plasma concentration ratios (based on AUC0-inf) of 0.682 in rats after a single oral dose.

A member of the class of phenylureas that is urea in which a hydrogen attached to one of the nitrogens is replaced by a 2,6-dichloro-3,5-dimethoxyphenyl group, while the hydrogens attached to the other nitrogen are replaced by a methyl group and a 6-{[4-(4-ethylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl group. It is a potent and selective fibroblast growth factor receptor inhibitor.


cholangiocarcinoma

A carcinoma that arises from the intrahepatic biliary tree (intrahepatic cholangiocarcinoma) or from the junction, or adjacent to the junction, of the right and left hepatic ducts (hilar cholangiocarcinoma). Grossly, the malignant lesions are solid, nodular, and grayish. Morphologically, the vast majority of cases are adenocarcinomas. Signs and symptoms include malaise, weight loss, right upper quadrant abdominal pain, and night sweats. Early detection is difficult and the prognosis is generally poor.


Lybalvi

Samidorphan was first approved in combination with olanzapine by the FDA on May 28, 2021, under the name LYBALVI. The mechanism of action of samidorphan could be mediated through opioid receptor antagonism.


bipolar I disorder

A bipolar disorder that is characterized by at least one manic or mixed episode.


Sotorasib

Sotorasib is an inhibitor of KRASG12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRASG12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS. Sotorasib blocked KRAS signaling, inhibited cell growth, and promoted apoptosis only in KRAS G12C tumor cell lines. Sotorasib inhibited KRASG12C in vitro and in vivo with minimal detectable off-target activity. In mouse tumor xenograft models sotorasib-treatment led to tumor regressions and prolonged survival and was associated with anti-tumor immunity in KRAS G12C models.

A pyridopyrimidine that is pyrido[2,3-d]pyrimidin-2(1H)-one substituted by 4-methyl-2-(propan-2-yl)pyridin-3-yl, (2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl, fluoro and 2-fluoro-6-hydroxyphenyl groups at positions 1, 4, 6 and 7, respectively. It is approved for the treatment of patients with non-small cell lung cancer having KRAS(G12C) mutations.


Ibrexafungerp

Ibrexafungerp, a triterpenoid antifungal agent, inhibits glucan synthase, an enzyme involved in the formation of 1,3-beta-D-glucan, an essential component of the fungal cell wall. Ibrexafungerp has concentration-dependent fungicidal activity against Candida species as measured by time kill studies. Ibrexafungerp retains in vitro antifungal activity when tested at pH 4.5 (the normal vaginal pH).


Erdheim-Chester disease

Erdheim-Chester disease (ECD), a non-Langerhans form of histiocytosis, is a multisystemic disease characterized by various manifestations such as skeletal involvement with bone pain, exophthalmos, diabetes insipidus, renal impairment and central nervous system (CNS) and/or cardiovascular involvement.


Chronic cough

A persistent cough, defined as a cough lasting longer than eight weeks in adults or longer than four weeks in children.


chronic hiccup

Chronic hiccup is a rare movement disorder characterized by involuntary spasmodic contractions of the inspiratory muscles synchronized with larynx closure lasting for more than 48 hours.


Intestinal hemorrhage due to angiodysplasia of intestine


Gastric hemorrhage due to angiodysplasia of stomach


traumatic encephalopathy

Encephalopathy resulting from trauma.


Cannabis hyperemesis syndrome co-occurrent and due to cannabis abuse


Cannabis hyperemesis syndrome co-occurrent and due to cannabis dependence


hypokalemic periodic paralysis

Hypokalemic periodic paralysis (hypoPP) is characterised by episodes of muscle paralysis lasting from a few to 24-48 hours and associated with a fall in blood potassium levels.


Overdose of beta-adrenergic blocking drug


Nerve injury

Injury to nervous tissue.


mucositis

Inflammation of the mucous membranes.


viral myocarditis

Myocarditis that is caused by an infection with a viral agent.


Mastalgia

Pain in the breast.


complex regional pain syndrome

Complex regional pain syndrome (CRPS) is a rare neurologic disease painful progressive condition that corresponds to a group of disorders characterized by a disproportionate spontaneous or stimulus-induced pain, accompanied by a variably mixed myriad of autonomic and motor disorders including symptoms such as swelling, allodynia, skin blood supply and trophic disturbances. CRPS most often affects one of the arms, legs, hands, or feet and usually occurs after an injury or trauma to that limb.


Sexual dysfunction due to substance

A disorder characterized by clinically significant sexual dysfunction (including impaired desire, impaired arousal, impaired orgasm, or sexual pain) that is fully explained by substance use.


Night sweats

Occurrence of excessive sweating during sleep.


Neuropathic Pain

Chronic pain caused by damage to nerve fibers.  It is usually associated with tissue injury.


Nightmares associated with chronic post-traumatic stress disorder


AMIVANTAMAB

Amivantamab-vmjw is a bispecific antibody that binds to the extracellular domains of EGFR and MET. In in vitro and in vivo studies amivantamab-vmjw was able to disrupt EGFR and MET signaling functions through blocking ligand binding and, in exon 20 insertion mutation models, degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells also allows for targeting of these cells for destruction by immune effector cells, such as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity ( ADCC) and trogocytosis mechanisms, respectively.


Non-small cell lung cancer with mutation in epidermal growth factor receptor


ADUCANUMAB

Aducanumab-avwa is a human, immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. The accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer’s disease. ADUHELM reduces amyloid beta plaques, as evaluated in Studies 1, 2, and 3.


Finerenone

Finerenone is a nonsteroidal, selective antagonist of the mineralocorticoid receptor (MR), which is activated by aldosterone and cortisol and regulates gene transcription. Finerenone blocks MR mediated sodium reabsorption and MR overactivation in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, and blood vessels) tissues. MR overactivation is thought to contribute to fibrosis and inflammation. Finerenone has a high potency and selectivity for the MR and has no relevant affinity for androgen, progesterone, estrogen, and glucocorticoid receptors.


Chronic kidney disease due to type 2 diabetes mellitus


Fexinidazole

Studies with Trypanosoma brucei and other protozoans suggest that, like for other nitrocontaining drugs, the nitroreductase (NTR) enzyme plays an important role in the bioactivation of fexinidazole resulting in generation of reactive amines and damage to DNA and proteins. The activity of fexinidazole and its metabolites (M1 and M2) is trypanocidal and appears to be concentration and time dependent. However, the precise mechanism by which fexinidazole and the two metabolites exhibit activity against T. brucei is not known.


Belumosudil is an inhibitor of rho-associated, coiled-coil containing protein kinase (ROCK) which inhibits ROCK2 and ROCK1 with IC50 values of approximately 100 nanoM and 3 microM, respectively. Belumosudil downregulated proinflammatory responses via regulation of STAT3/STAT5 phosphorylation and shifting Th17/Treg balance in ex-vivo or in vitro-human T cell assays. Belumosudil also inhibited aberrant pro-fibrotic signaling, in vitro. In vivo, belumosudil demonstrated activity in animal models of chronic GVHD.


Odevixibat

Odevixibat is a reversible inhibitor of the ileal bile acid transporter (IBAT). It decreases the reabsorption of bile acids (primarily the salt forms) from the terminal ileum. Pruritus is a common symptom in patients with PFIC and the pathophysiology of pruritus in patients with PFIC is not completely understood. Although the complete mechanism by which odevixibat improves pruritus in PFIC patients is unknown, it may involve inhibition of the IBAT, which results in decreased reuptake of bile salts, as observed by a decrease in serum bile acids.


progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin.


Belzutifan

Belzutifan is an inhibitor of hypoxia-inducible factor 2 alpha (HIF-2alpha), with potential antineoplastic activity. HIF-2alpha is a transcription factor that plays a role in oxygen sensing by regulating genes that promote adaptation to hypoxia. Under normal oxygen levels, HIF-2alpha is targeted for ubiquitin-proteasomal degradation by VHL protein. Lack of functional VHL protein results in stabilization and accumulation of HIF-2alpha. Upon stabilization, HIF-2alpha translocates into the nucleus and interacts with hypoxia-inducible factor 1 beta (HIF-1beta) to form a transcriptional complex that induces expression of downstream genes, including genes associated with cellular proliferation, angiogenesis, and tumor growth. Belzutifan binds to HIF-2alpha, and in conditions of hypoxia or impairment of VHL protein function, belzutifan blocks the HIF-2alpha-HIF-1beta interaction, leading to reduced transcription and expression of HIF-2alpha target genes. In vivo, belzutifan demonstrated anti-tumor activity in mouse xenograft models of renal cell carcinoma.