Integrative Multi-Omics Approaches Reveal Selectivity Profiles and Molecular Mechanisms of FIIN-2, a Covalent FGFR Inhibitor.

ABSTRACT: Fibroblast growth factor receptor (FGFR) inhibitors are emerged as an important class of targeted therapies in oncology, targeting key pathways associated with tumor growth, angiogenesis, and resistance to conventional treatments. FIIN-2, the first irreversible covalent pan-FGFR inhibitor, has shown promise in overcoming resistance due to gatekeeper mutations; however, its selectivity and molecular mechanisms in tumors remain poorly understood. In this study, an FIIN-2 chemical probe is designed and synthesized to identify both established and novel targets in hepatocellular carcinoma (HCC) via chemoproteomic profiling. An integrative multi-omics approach, including chemoproteomic, phosphoproteomic, transcriptomic, and proteomic analyses, is utilized to elucidate the full spectrum of targe

SUBMITTER: Fu Y 

PROVIDER: S-EPMC11984845 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature