c-Met/HGFR Inhibitor

Ensartinib (X-396) is a BBB-permeable and dual ALK/MET inhibitor with IC₅₀s of <0.4 nM and 0.74 nM, respectively.

Merestinib (LY2801653) is a potent, orally bioavailable c-Met inhibitor (K_i=2 nM) with anti-tumor activities. Merestinib (LY2801653) also has potent activity against MST1R (IC₅₀=11 nM), FLT3 (IC₅₀=7 nM), AXL (IC₅₀=2 nM), MERTK (IC₅₀=10 nM), TEK (IC₅₀=63 nM), ROS1, DDR1/2 (IC₅₀=0.1/7 nM) and MKNK1/2 (IC₅₀=7 nM).

Altiratinib (DCC-2701) is a multi-targeted kinase inhibitor with IC₅₀s of 2.7, 8, 9.2, 9.3, 0.85, 4.6, 0.83 nM for MET, TIE2, VEGFR2, FLT3, Trk1, Trk2, and Trk3 respectively.

Tilatamig samrotecan (AZD9592) is an anti-EGFR/c-MET antibody-drug conjugate (ADC). Tilatamig samrotecan consists of an anti-EGFR/c-MET antibody with the drug-linker conjugate being AZ14170133 (HY-145399) (a topoisomerase I (TOP1i) inhibitor payload). Tilatamig samrotecan induces multiple DNA damage response pathway markers (like ATM, ATR, γH2AX). Tilatamig samrotecan selectively binds to EGFR and c-MET, delivering the cytotoxic payload. Tilatamig samrotecan exerts anti-tumor activity in vivo. Tilatamig samrotecan can be used for non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) research.

Golvatinib (E-7050) is a potent dual inhibitor of both c-Met and VEGFR2 kinases with IC₅₀s of 14 and 16 nM, respectively.

Glumetinib (SCC244) is a highly selective, orally bioavailable, ATP-competitive c-Met inhibitor with an IC₅₀ of 0.42 nM. Glumetinib has greater than 2400-fold selectivity for c-Met over those 312 kinases evaluated, including the c-Met family member RON and highly homologous kinases Axl, Mer, TyrO3. Antitumor activity.

Bozitinib (PLB-1001) is a highly selective c-MET kinase inhibitor with blood-brain barrier permeability. Bozitinib (PLB-1001) is a ATP-competitive small-molecule inhibitor, binds to the conventional ATP-binding pocket of the tyrosine kinase superfamily.

SCR-1481B1 (Metatinib anhydrous; c-Met inhibitor 2) is an inhibitor of the N-terminal fragment of Gasdermin D (GSDMD), with an IC₅₀ of 1.04 μM and a K_a of 0.42 μM in mice. SCR-1481B1 effectively blocks GSDMD-NT oligomerization and pore formation, inhibits GSDMD-mediated pyroptosis (Pyroptosis), preserves mitochondrial integrity, and reduces proinflammatory cytokine secretion. SCR-1481B1 also inhibits angiogenesis, exerts GSDMD-independent antitumor effects, and enhances the infiltration of antitumor immune cells. SCR-1481B1 is also an inhibitor targeting to c-MET and VEGFR2, can be used in studies related to melanoma and sepsis.

Ficlatuzumab is a monoclonal antibody (McAb) targeting human hepatocyte growth factor (HGF). Ficlatuzumab blocks the activation of the HGF/c-Met signaling pathway, and inhibits c-Met receptor-mediated cancer cell proliferation, migration, and invasion.

Ensartinib dihydrochloride (X-396 dihydrochloride) is a BBB-permeable and dual ALK/MET inhibitor with IC₅₀s of <0.4 nM and 0.74 nM, respectively.

Capmatinib (INC280; INCB28060) dihydrochloride hydrate is a potent, orally active, selective, and ATP competitive c-Met kinase inhibitor (IC₅₀=0.13 nM). Capmatinib dihydrochloride hydrate can inhibit phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT, FAK, GAB1, and STAT3/5. Capmatinib dihydrochloride hydrate potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis. Antitumor activity. Capmatinib dihydrochloride hydrate is largely metabolized by CYP3A4 and aldehyde oxidase.

JNJ-38877605 is an orally active ATP-competitive inhibitor of c-Met with an IC₅₀ of 4 nM, 600-fold selective for c-Met than 200 other tyrosine and serine-threonine kinases. JNJ-38877605 inhibits c-Met phosphorylation and regulates lipid accumulation. JNJ-38877605 can be used for tumor and metabolic disease reseach.

SGX523 is a exquisitely selective and ATP-competitive MET inhibitor. SGX523 potently inhibits MET with an IC₅₀ of 4 nM and is >1,000-fold selective versus other protein kinases. Antitumor activity.

Risvodetinib (IkT-148009) is an orally active, selective and brain-penetrant protein tyrosine kinase inhibitor, displaying excellent target efficacy against c-Abl1, c-Abl2/Arg with IC₅₀ values of 33 nM, 14 nM, respectively. Risvodetinib suppresses c-Abl activation and substantially protects dopaminergic neurons from degeneration in mouse models of both inherited and sporadic Parkinson’s disease (PD), which is promising for research in the field of PD.

c-Kit-IN-1 is a potent inhibitor of c-Kit and c-Met with IC₅₀s of <200 nM.

Amuvatinib (MP470) is an orally bioavailable multi-targeted tyrosine kinase inhibitor with potent activity against mutant c-Kit, PDGFRα, Flt3, c-Met and c-Ret. Amuvatinib (MP470) is also a DNA repair suppressor through suppression of DNA repair protein RAD51, thereby disrupting DNA damage repair. Antineoplastic activity.

Rilotumumab (AMG 102) is an anti-HGF (anti-hepatocyte growth factor) monoclonal antibody, inhibits HGF/MET-driven signaling. Rilotumumab shows anti-tumor activity, and can be used in castration-resistant prostate cancer (CRPC) and solid tumor research.

BMS-794833 is a VEGFR2 and Met inhibitor extracted from patent WO2009094417, compound example 1; has IC₅₀s of 15 and 1.7 nM, respectively.

MAPK-IN-2 (compound 3h) is a potent MAPK inhibitor with antineoplastic activity. MAPK-IN-2 inhibits cancer cell proliferation among serval cancer cell lines, and suppresses MAPK pathway with potant efficacy (EGFR^WT IC₅₀=281 nM, c-MET IC₅₀=205 nM, B-RAF^WT IC₅₀=112 nM, and CDK4/6 IC₅₀=95 and 184 nM, respectively). MAPK-IN-2 even shows a remarkable potency against mutated EGFR and B-RAF (EGFR^T790M IC₅₀=69 nM and B-RAF^V600E IC₅₀=83 nM).

SRI 31215 (TFA) is a Matriptase/Hepsin/hepatocyte growth factor activator (HGFA) triplex inhibitor and mimics the activity of HAI-1/2 (endogenous inhibitors of HGF activation). SRI 31215 has potent inhibitory activity against matriptase, hepsin and HGFA with IC₅₀ values of 0.69 μM, 0.65 μM and 0.30 μM, respectively. SRI 31215 can be used for the research of cancer.