NVS

Alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα.

Asciminib is an ABL/BCR-ABL1 tyrosine kinase inhibitor. Asciminib inhibits the ABL1 kinase activity of the BCR::ABL1 fusion protein, by binding to the ABL myristoyl pocket.

Bosutinib is a TKI. Bosutinib inhibits the BCR-ABL kinase that promotes CML; it is also an inhibitor of Src-family kinases including Src, Lyn, and Hck. Bosutinib inhibited 16 of 18 imatinib-resistant forms of BCR-ABL kinase expressed in murine myeloid cell lines.

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 (PSGL-1).

Dabrafenib is an inhibitor of some mutated forms of BRAF kinases with in vitro IC 50 values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes, respectively.

Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase.

Taxane chemotherapy that stabilizes microtubules and arrests mitosis. Used in breast, prostate, NSCLC, head and neck, and gastric cancers.

Anti-IL-4Rα monoclonal antibody (Dupixent) that blocks both IL-4 and IL-13 signaling. Approved in atopic dermatitis, asthma, eosinophilic esophagitis, chronic rhinosinusitis with nasal polyps, and prurigo nodularis.

Eltrombopag is a TPO-receptor agonist that interacts with the transmembrane domain of the human TPO-receptor (also known as cMpl) and initiates signaling cascades that induce proliferation and differentiation of megakaryocytes leading to increased platelet production.

Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers and in tuberous sclerosis complex (TSC).

Breast cancer cell growth may be estrogen-dependent. Aromatase is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women.

Fingolimod is metabolized by sphingosine kinase to the active metabolite, fingolimod-phosphate. Fingolimod-phosphate is a sphingosine 1-phosphate receptor modulator, and binds with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5.

Injectable selective estrogen receptor degrader (Faslodex) that binds and degrades ERα. Used in HR-positive metastatic breast cancer.

ZOLADEX is a synthetic decapeptide analogue of GnRH. ZOLADEX acts as an inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation.

Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in CML.

Inclisiran is a double-stranded small interfering ribonucleic acid (siRNA), conjugated on the sense strand with triantennary N-Acetylgalactosamine (GalNAc) to facilitate uptake by hepatocytes.

Inclisiran is a double-stranded small interfering ribonucleic acid (siRNA), conjugated on the sense strand with triantennary N-Acetylgalactosamine (GalNAc) to facilitate uptake by hepatocytes.

The mechanism(s) by which REBIF (interferon beta-1a) exerts its therapeutic effects in patients with multiple sclerosis is unknown.

Oral selective Factor B inhibitor (Fabhalta) that blocks the alternative complement pathway. Approved in paroxysmal nocturnal hemoglobinuria and IgA nephropathy.

Oral non-steroidal aromatase inhibitor (Femara) that blocks estrogen synthesis. Standard endocrine therapy in HR-positive postmenopausal breast cancer.

Leuprolide acetate, a gonadotropin releasing hormone (GnRH) agonist, acts as an inhibitor of gonadotropin secretion when given continuously in therapeutic doses.

Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of ABL protein.

The precise mechanism by which ocrelizumab exerts its therapeutic effects in multiple sclerosis is unknown, but is presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes.

The precise mechanism by which ofatumumab exerts its therapeutic effects in multiple sclerosis is unknown, but is presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes.

Asthma, Chronic Rhinosinusitis with Nasal Polyps, and IgE-Mediated Food Allergy Omalizumab inhibits the binding of IgE to the high-affinity IgE receptor (FcεRI) on the surface of mast cells, basophils, and dendritic cells, resulting in FcεRI down-regulation on these cells.

Onasemnogene abeparvovec 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.

Onasemnogene abeparvovec 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.

Pertuzumab targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2) and, thereby, blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3, and HER4.

Remibrutinib is an oral, small molecule kinase inhibitor that inhibits Bruton’s tyrosine kinase (BTK). BTK is an intracellular protein expressed in mast cells, basophils, B cells, macrophages, and thrombocytes.

Oral selective CDK4/6 inhibitor (Kisqali) that blocks cell-cycle progression. Approved in HR-positive HER2-negative metastatic and adjuvant breast cancer.

Oral selective JAK1/JAK2 inhibitor (Jakafi) that blocks JAK-STAT signaling. Approved in myelofibrosis, polycythemia vera, GVHD, and topically in atopic dermatitis.

Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses.

Siponimod is an 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.

Teriflunomide, an immunomodulatory agent with anti-inflammatory properties, inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme involved in de novo pyrimidine synthesis.

KYMRIAH is a CD19-directed genetically modified autologous T cell immunotherapy which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells.

Oral selective MEK1/2 inhibitor (Mekinist) that blocks MAPK pathway signaling. Approved in BRAF-mutant melanoma, NSCLC, and thyroid cancer, typically combined with dabrafenib.

Anti-HER2 monoclonal antibody (Herceptin) that binds the extracellular domain of HER2, blocking signaling and triggering ADCC. Standard of care in HER2-positive breast and gastric cancers.

Anti-APRIL monoclonal antibody (Novartis) that blocks B-cell survival signaling. Phase 3 in IgA nephropathy.

Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis.

Anti-PD-L1 monoclonal antibody (Tecentriq) that blocks PD-L1, restoring T-cell anti-tumor activity. Approved in NSCLC, SCLC, urothelial, and hepatocellular carcinoma.

Atrasentan is an ET A receptor antagonist (Ki = 0.034 nM) with >1800-fold selectivity for the ET A receptor compared to the endothelin type B receptor (Ki = 63.3 nM). Endothelin (ET)-1 is thought to contribute to the pathogenesis of IgAN via the ET A R.

Azacitidine is a pyrimidine nucleoside analog of cytidine. Azacitidine is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow.

Benznidazole is a nitroimidazole antimicrobial drug [see Microbiology ( 12.4 )] .

Oral 5-fluorouracil prodrug activated to 5-FU in tumor tissue. Used in colorectal, breast, and gastric cancers, often combined with oxaliplatin or platinum.

Capmatinib is a kinase inhibitor that targets MET, including the mutant variant produced by exon 14 skipping. MET exon 14 skipping results in a protein with a missing regulatory domain that reduces its negative regulation leading to increased downstream MET signaling.

Chimeric anti-EGFR monoclonal antibody (Erbitux) that blocks EGFR signaling and triggers ADCC. Approved in metastatic colorectal cancer (KRAS wild-type) and head and neck cancer.

Darolutamide is an androgen receptor (AR) inhibitor. Darolutamide competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. A major metabolite, ketodarolutamide, exhibited similar in vitro activity to darolutamide.

Decitabine is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis.

Oral second-generation androgen receptor antagonist (Xtandi) that blocks AR signaling. Approved in metastatic and non-metastatic castration-resistant prostate cancer.

Epipodophyllotoxin chemotherapy that inhibits topoisomerase II. Used in small cell lung cancer, testicular cancer, and lymphomas.

Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP.

The epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells and plays a role in the processes of cell growth and proliferation.

Ibrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK). Ibrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity.

Oral covalent KRAS G12C inhibitor (Novartis) under investigation in KRAS G12C-mutant solid tumors including NSCLC.

Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks.

Osimertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR), which binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletions) at approximately 9-fold lower concentrations than wild-type.

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

Chimeric anti-CD20 monoclonal antibody (Rituxan) that depletes B cells via ADCC, CDC, and apoptosis. Foundational in B-cell lymphomas, CLL, rheumatoid arthritis, and ANCA vasculitis.

Anti-PD-1 monoclonal antibody (Tevimbra) engineered to minimize FcγR binding. Approved in esophageal squamous cell carcinoma, NSCLC, and other cancers.

Oral allosteric SHP2 phosphatase inhibitor (Novartis) that blocks RAS-MAPK signaling. Under investigation in RAS/EGFR-driven solid tumors, often combined with KRAS or EGFR inhibitors.

Oral dual EZH1/EZH2 inhibitor (Constellation/Morphic) that blocks PRC2-mediated gene silencing. Under investigation in lymphomas and solid tumors.

Oral selective BCL-2 inhibitor (Venclexta) that restores apoptosis in cancer cells. Approved for chronic lymphocytic leukemia, acute myeloid leukemia, and small lymphocytic lymphoma.