c-Met/HGFR Inhibitor

Afatinib (BIBW 2992) is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC₅₀ values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFR^wt, EGFR^L858R, EGFR^L858R/T790M and HER2, respectively. Afatinib can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer.

Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive ALK and c-Met inhibitor with IC₅₀s of 20 and 8 nM, respectively. Crizotinib inhibits tyrosine phosphorylation of NPM-ALK and tyrosine phosphorylation of c-Met with IC₅₀s of 24 and 11 nM in cell-based assays, respectively. Crizotinib is also a ROS1 inhibitor. Crizotinib has effective tumor growth inhibition.

Cabozantinib is a potent and orally active inhibitor of VEGFR2 and MET, with IC₅₀ values of 0.035, and 1.3 nM, respectively. Cabozantinib displays strong inhibition of KIT, RET, AXL, TIE2, and FLT3 (IC₅₀=4.6, 5.2, 7, 14.3, and 11.3 nM, respectively). Cabozantinib shows antiangiogenic activity. Cabozantinib disrupts tumor vasculature and promotes tumor and endothelial cell apoptosis.

Capmatinib (INC280; INCB28060) is a potent, orally active, selective, and ATP competitive c-Met kinase inhibitor (IC₅₀=0.13 nM). Capmatinib 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 potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis. Antitumor activity. Capmatinib is largely metabolized by CYP3A4 and aldehyde oxidase.

Telisotuzumab vedotin (ABBV-399) (Teliso-V) is an anti-c-Met antibody-drug conjugate. Telisotuzumab vedotin consists of an anti-c-Met monoclonal antibody Telisotuzumab (ABT-700) (HY-P99391) and Monomethyl Auristatin E (HY-15162). Telisotuzumab vedotin exerts antitumor activity with acceptable toxicity in vivo. Telisotuzumab vedotin can be used for non-small cell lung cancer (NSCLC) research.

Telisotuzumab (ABT-700) is a bivalent humanized IgG1 anti-c-Met monoclonal antibody. Telisotuzumab binds cellular c-Met and disrupts its productive dimerization and activation induced by HGF or by the high density of c-Met on the cell surface independent of ligand. Telisotuzumab induces apoptosis. Telisotuzumab can be used for the study of cancers harboring amplified MET, such as gastric and lung cancers.

Tepotinib (EMD-1214063) is an orally active and highly selective, reversible, ATP-competitive c-Met inhibitor with an IC₅₀ of 3 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Tepotinib inhibits c-Met phosphorylation and induces autophagy. Tepotinib has antitumor effects.

Zongertinib (BI 1810631) is a potent and selective HER2 and EGFR tyrosine kinase inhibitor with IC₅₀ values of 13 nM and 579 nM, respectively. Zongertinib has antitumor activity and can be used in the study of multiple solid tumors.

Decanoic acid is a key component of the medium-chain triglyceride (MCT) found in coconut oil. Decanoic acid is a brain-penetrant and non-competitive inhibitor of AMPA receptor showing antiseizure activity in rats. Decanoic acid reduces tyrosinase activity and inhibits melanosome maturation. Decanoic acid suppresses the phosphorylation of c-Met and induced apoptosis in hepatocellular carcinoma (HCC) cells by inhibiting the expression of various oncogenic proteins, which is promising for research in the field of mTORC1 signaling, HCC and epilepsy.

BMS 777607 (BMS 817378) is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC₅₀s of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM, respectively, and 40-fold more selective for Met-related targets than Lck, VEGFR-2, and TrkA/B, with more than 500-fold greater selectivity versus all other receptor and non receptor kinases.

Afatinib (BIBW 2992) dimaleate is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC₅₀ values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFR^wt, EGFR^L858R, EGFR^L858R/T790M and HER2, respectively. Afatinib dimaleate can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer.

PHA-665752 is a selective, ATP-competitive, and active-site inhibitor of the catalytic activity of c-Met kinase (K_i=4 nM; IC₅₀=9 nM). PHA-665752 exhibits >50-fold selectivity for c-Met compared with a panel of diverse tyrosine and serine-threonine kinases. PHA-665752 induces apoptosis and cell cycle arrest, and exhibits cytoreductive antitumor activity.

Zanzalintinib (XL092) is an orally active, ATP-competitive inhibitor of multiple receptor tyrosine kinases (RTKs) including MET, VEGFR2, AXL and MER, with IC₅₀s in cell-based assays of 15 nM, 1.6 nM, 3.4 nM, 7.2 nM respectively. Zanzalintinib exhibits anti-tumor activity. Zanzalintinib has the potential for kinase-dependent diseases and conditions research.

Foretinib is a multi-target tyrosine kinase inhibitor with IC₅₀s of 0.4 nM and 0.9 nM for Met and KDR.

Onartuzumab (MetMAb) is a unique, humanized and affinity-matured monovalent (one-armed) monoclonal antibody against the MET receptor. Onartuzumab potently inhibits HGF binding and receptor phosphorylation and signaling. Onartuzumab has antibody-like pharmacokinetics and antitumor activity.

Tivantinib is a highly selective c-Met tyrosine kinase inhibitor with a K_i of 355 nM.

Emibetuzumab (LY2875358) is a humanized bivalent MET antibody (IgG4 type). Emibetuzumab shows high neutralization and internalization activities, resulting in inhibition of both HGF-dependent and HGF-independent MET pathway activation and tumor growth. Emibetuzumab can be used in study of cancer.

Crizotinib hydrochloride (PF-02341066 hydrochloride) is an orally bioavailable, selective, and ATP-competitive dual ALK and c-Met inhibitor with IC₅₀s of 20 and 8 nM, respectively. Crizotinib hydrochloride (PF-02341066 hydrochloride) inhibits tyrosine phosphorylation of NPM-ALK and tyrosine phosphorylation of c-Met with IC₅₀s of 24 and 11 nM in cell-based assays, respectively. It is also a ROS proto-oncogene 1 (ROS1) inhibitor. Crizotinib hydrochloride (PF-02341066 hydrochloride) has effective tumor growth inhibition.

SU11274 is a selective Met inhibitor with IC₅₀ of 10 nM, but has no effects on PGDFRβ, EGFR or Tie2.

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