c-met (mouse)

AMG-458 is a potent c-Met inhibitor with Ki of 1.2 nM, ~350-fold selectivity for c-Met than VEGFR2 in cells.

Crizotinib (PF-02341066) is an ATP-competitive small-molecule tyrosine kinase inhibitor of c-MET (IC50: 8 nM) and ALK (IC50: 20 nM) receptors.

KRC-00715 is an orally effective inhibitor of c-Met, exhibiting high selectivity with an IC50 of 9.0 nM. This compound specifically inhibits the growth of gastric cancer cell lines with high c-Met expression by inducing G1 S phase block, and reduces the activity of downstream signals, including Akt, Erk, and c-Met itself. In the gastric cancer cell line Hs746T, KRC-00715 demonstrates cytotoxicity with an IC50 of 39 nM and selectively inhibits the proliferation of cell lines that overexpress c-Met. Additionally, KRC-00715 decreases tumor size in Hs746T xenograft mouse models.

PROTACc-Met degrader-1 (Compound Met-DD4) is an orally effective PROTAC degrader targeting c-Met with a DC50 of 6.21 nM. It inhibits the proliferation of c-Met-addicted MKN-45 cells with an IC50 of 4.37 nM and causes cell cycle arrest in the G0 G1 phase. In a xenograft mouse model using MKN-45 cells, PROTACc-Met degrader-1 demonstrates antitumor activity.

CYY292 is a chemical compound acting as an inhibitor of PDGFRα, PDGFRβ, FGFR1, -2, and -3, with respective IC50 values of 5.35, 4.6, 28, 28, and 78 nM. It exhibits selectivity over FGFR4 (IC50 > 1,000 nM) while also targeting c-Kit, VEGFR2, VEGFR1, and IGF-1R (IC50 values of 67, 33, 36, and 75 nM, respectively). Additionally, CYY292 inhibits EGFR, BTK, Cdk4/cyclin D3, and MET with IC50 values of 128, 198, 214, and 396 nM, respectively. This compound demonstrates efficacy in arresting the proliferation of various osteosarcoma cell lines—MG-63, U2OS, MNNG/HOS, and Saos-2—with IC50s ranging from 0.72 to 1.36 µM. Moreover, CYY292 at 0.3 and 0.5 µM concentrations inhibits migration and invasion in glioblastoma cells (U87MG and LN-229) and, at a dose of 30 mg/kg, decreases tumor volume and enhances survival in a U87MG orthotopic mouse xenograft model.

Arylsulfonamide 64B (HIF inhibitor 64B), an inhibitor of the hypoxia-induced factor (HIF), not only suppresses hypoxia HIF-induced expression of c-Met and CXCR4 but also decreases primary tumor growth and metastasis in a uveal melanoma mouse model [1].

PARP1 c-Met-IN-1 (Compound 16) serves as a selective dual inhibitor targeting both PARP1 and c-Met, demonstrating IC50 values of 3.3 nM and 32.2 nM, respectively. This compound effectively induces apoptosis and causes cell cycle arrest at the G2 M phase in MDA-MB-231 cells. Furthermore, PARP1 c-Met-IN-1 displays notable antitumor activity in mouse models [1].