2. Academic Validation
  3. Discovery of N-(4-(pyridin-4-yloxy)phenyl)-1,2-dihydropyridine-3-carboxamide derivatives as potential type II c-Met inhibitors

Discovery of N-(4-(pyridin-4-yloxy)phenyl)-1,2-dihydropyridine-3-carboxamide derivatives as potential type II c-Met inhibitors

  • Bioorg Med Chem. 2025 Sep 17:131:118394. doi: 10.1016/j.bmc.2025.118394.
Qingwang Xin 1,  Chao Fang 2,  Baojian Xing 1,  Jikang Du 1,  Simin Ren 3
Affiliations

Affiliations

  • 1 Department of Gastrointestinal surgery, BaoDing No.1 Hospital, Baoding 071000, China.
  • 2 Department of Geriatric Medicine, Affiliated Hospital of Hebei University, Baoding 071000, China.
  • 3 Department of Neurology, Affiliated Hospital of Hebei University, Baoding 071000, China. Electronic address: rsm8671@outlook.com.
PMID: 40975897 DOI: 10.1016/j.bmc.2025.118394
Abstract

The c-Met receptor tyrosine kinase plays a pivotal role in oncogenesis and tumor progression, with its dysregulation frequently contributing to therapeutic resistance. Through structure-based virtual screening of the ChemDiv database, we prioritized 20 candidates, including type II and III inhibitors, with compounds A3 and A17 emerging as initial hits. Subsequent optimization yielded A30, a hybrid scaffold inhibitor demonstrating potent activity against both wild-type and mutant c-Met, comparable to the reference inhibitor BMS-777607. Cellular assays revealed that A30 significantly suppressed proliferation, migration, and colony formation in NCI-H1993 and HCT-116 cells, while inducing Apoptosis. These findings highlight A30 as a promising lead compound for targeting c-Met-driven resistance.

Keywords

Anti-tumor; Receptor tyrosine kinase; c-Met.

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