2. Academic Validation
  3. Discovery of LAH-1 as potent c-Met inhibitor for the treatment of non-small cell lung cancer

Discovery of LAH-1 as potent c-Met inhibitor for the treatment of non-small cell lung cancer

  • J Enzyme Inhib Med Chem. 2024 Dec;39(1):2286435. doi: 10.1080/14756366.2023.2286435.
Lijie Sima 1,  Zhongyuan Wang 2,  Ling Yu 3,  Youli Hou 4,  Dongsheng Zhao 4,  Bilan Luo 4,  Weike Liao 4,  Xinfu Liu 1
Affiliations

Affiliations

  • 1 Department of Hematology and Oncology, The Affiliated Shaoyang Hospital, Hengyang Medical School, University of South China (Shaoyang Central Hospital), Shaoyang, China.
  • 2 Department of Pharmacy, Guizhou Provincial People's Hospital, Guiyang, China.
  • 3 Department of Pharmacy, Guiyang Healthcare Vocational University, Guiyang, China.
  • 4 Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, China.
PMID: 38078363 DOI: 10.1080/14756366.2023.2286435
Abstract

ABSTRCTDysregulated HGF/c-Met pathway has been implicated in multiple human cancers and has become an attractive target for Cancer intervention. Herein, we report the discovery of N-(3-fluoro-4-((2-(3-hydroxyazetidine-1-carboxamido)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-4-methyl-6-oxo-1,6-dihydropyridazine-3-carboxamide (LAH-1), which demonstrated nanomolar MET kinase activity as well as desirable antiproliferative activity, especially against EBC-1 cells. Mechanism studies confirmed the effects of LAH-1 on modulation of HGF/c-Met pathway, induction of cell Apoptosis, inhibition on colony formation as well as cell migration and invasion. In addition, LAH-1 also showed desirable in vitro ADME properties as well as acceptable in vivo PK parameters. The design, synthesis, and characterisation of LAH-1 are described herein.

Keywords

LAH-1; NSCLC; antitumor activity; c-Met.

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