Identification of Novel Compounds That Bind to the HGF β-Chain In Silico, Verification by Molecular Mechanics and Quantum Mechanics, and Validation of Their HGF Inhibitory Activity In Vitro.

ABSTRACT: The development of small-molecule drugs targeting growth factors for cancer therapy remains a significant challenge, with only limited successful cases. We attempted to identify hepatocyte growth factor (HGF) inhibitors as novel anti-cancer small-molecule drugs. To identify compounds that bind to the β-chain of HGF and inhibit signaling through HGF and its receptor Met interaction, we performed a hierarchical in silico drug screen using a three-dimensional compound structure library (Chembridge, 154,118 compounds). We experimentally tested whether 10 compounds selected as candidates for novel anticancer agents exhibit inhibition of HGF activity. Compounds 6 and 7 potently inhibited Met phosphorylation in the human EHEMES-1 cell line, with IC₅₀ values of 20.4 and 11

SUBMITTER: Suzuki K 

PROVIDER: S-EPMC12029800 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature