c-MET

DFX117 is a selective, orally active inhibitor targeting PI3Kα and c-Met tyrosine kinase. This compound effectively inhibits the PI3K/Akt/mTOR pathway, demonstrating significant antiproliferative activity against cancer cell lines such as NCI-H1975, NCI-H1993, and HCC827, with IC50 values ranging from 0.02 to 0.08 µM. DFX117 induces cell cycle arrest at the G0/G1 phase and promotes apoptosis in A549 and NCI-H1975 cells. Additionally, DFX117 exhibits notable antitumor efficacy in murine models, making it a valuable tool for cancer research.

Capmatinib hydrochloride is a selective c-MET kinase inhibitor that competitively targets ATP (IC50 = 0.13 nM). It effectively inhibits the phosphorylation of c-MET and its downstream signaling pathways, including ERK1/2, AKT, FAK, GAB1, and STAT3/5. Capmatinib hydrochloride demonstrates potent antitumor activity by inhibiting c-MET-dependent tumor cell proliferation and migration, as well as inducing apoptosis. This compound is primarily metabolized by CYP3A4 and aldehyde oxidase, making it relevant for studies in cancer research and therapeutic development.

ABN401 is a selective ATP-competitive inhibitor of c-MET, exhibiting an IC50 of 10 nM. This compound demonstrates cytotoxic effects on MET-addicted cancer cells, with IC50 values ranging from 2 to 43 nM. ABN401 has shown oral bioavailability in preclinical models, with 42.1% to 56.2% in rats and 27.4% to 37.7% in dogs, and possesses significant antitumor activity, making it a valuable tool for cancer research and therapeutic development.

EGFR/c-Met-IN-1 is a dual inhibitor targeting both EGFR and c-Met, with IC50 values of 68.1 nM for EGFRL858R and 0.26 nM for c-Met. This compound induces apoptosis and causes cell cycle arrest in A549-P cells by downregulating the phosphorylation of EGFR, c-Met, and downstream AKT pathways. EGFR/c-Met-IN-1 demonstrates significant tumor growth inhibition in vitro and in vivo, making it a valuable reagent for cancer research focused on targeting these pathways.

EGFR-IN-8 is a dual inhibitor of the epidermal growth factor receptor (EGFR) and c-Met, demonstrating potential efficacy against EGFR TKI-resistant non-small cell lung cancer (NSCLC). This compound offers a novel approach for effectively targeting resistance mechanisms in NSCLC, providing a valuable tool for oncological research and drug development. Its unique pharmacological profile positions it as a promising candidate for further investigation in cancer therapy.