Design, Synthesis and Biological Activity Study of γ-Aminobutyric Acid (GABA) Derivatives Containing Bridged Bicyclic Skeletons as BCAT1 Inhibitors.

ABSTRACT: Branched-chain amino acid aminotransferases (BCATs), existing as the two isoforms BCAT1 and BCAT2, are responsible for the catabolism of branched-chain amino acids (BCAAs) and are highly upregulated and implicated in a diverse range of cancers. BCAT1 inhibitors represent a potential class of therapeutic agents for cancers; however, none have yet progressed to clinical development. Our earlier research identified WQQ-345 as a novel BCAT1 inhibitor featuring a unique bridged bicyclic skeleton and demonstrating both in vitro and in vivo antitumor activity against tyrosine kinase inhibitor (TKI)-resistant lung cancer with high BCAT1 expression. In the present study, we proceeded to modify the structure of WQQ-345 by two-round structure-activity relationship (SAR) exploration, lea

SUBMITTER: Luo W 

PROVIDER: S-EPMC11858294 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature