Design, Synthesis, and Biological Evaluation of 5',7-Disubstituted 7-Deaza-adenosine Analogues as Irreversible Pan-FGFR Inhibitors.

ABSTRACT: Background/Objectives: Fibroblast growth factor receptors (FGFRs) are frequently dysregulated in diverse cancers and represent important therapeutic targets. Here, we report the design and synthesis of a novel nucleoside-based scaffold which enables irreversible pan-FGFR inhibition as a potential anticancer strategy. Methods: A series of nucleoside analogues was synthesized and assessed through structure-activity relationship studies. Structural analyses, including X-ray co-crystallography and molecular dynamics simulations, were performed to define key determinants of potency and selectivity. Biochemical assays against FGFR1-4 proteins, cellular antiproliferative assays in HCT116 (FGFR1 amplification) and RT4 (FGFR3-TACC3) models, metabolic stability evaluations and covalent

SUBMITTER: Park JH 

PROVIDER: S-EPMC12655421 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature