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Ref Type Journal Article
PMID (37588207)
Authors Bi Y, Zheng R, Hu J, Shi R, Shi J, Wang Y, Wang P, Jiang W, Kim G, Liu Z, Li X, Lin L
Title A novel FGFR1 inhibitor CYY292 suppresses tumor progression, invasion, and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis.
Abstract Text Glioblastoma (GBM) is a malignant brain tumor that grows quickly, spreads widely, and is resistant to treatment. Fibroblast growth factor receptor (FGFR)1 is a receptor tyrosine kinase that regulates cellular processes, including proliferation, survival, migration, and differentiation. FGFR1 was predominantly expressed in GBM tissues, and FGFR1 expression was negatively correlated with overall survival. We rationally designed a novel small molecule CYY292, which exhibited a strong affinity for the FGFR1 protein in GBM cell lines in vitro. CYY292 also exerted an effect on the conserved Ser777 residue of FGFR1. CYY292 dose-dependently inhibited cell proliferation, epithelial-mesenchymal transition, stemness, invasion, and migration in vitro by specifically targeting the FGFR1/AKT/Snail pathways in GBM cells, and this effect was prevented by pharmacological inhibitors and critical gene knockdown. In vivo experiments revealed that CYY292 inhibited U87MG tumor growth more effectively than AZD4547. CYY292 also efficiently reduced GBM cell proliferation and increased survival in orthotopic GBM models. This study further elucidates the function of FGFR1 in the GBM and reveals the effect of CYY292, which targets FGFR1, on downstream signaling pathways directly reducing GBM cell growth, invasion, and metastasis and thus impairing the recruitment, activation, and function of immune cells.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
CYY292 CYY292 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
CYY292 CYY-292|CYY 292 FGFR1 Inhibitor 28 CYY292 is an Fgfr1 inhibitor, which reduces downstream signaling and potentially decreases tumor cell growth and metastasis (PMID: 37588207).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR1 positive glioblastoma sensitive CYY292 Preclinical - Cell line xenograft Actionable In a preclinical study, CYY292 inhibited Fgfr1 downstream signaling, proliferation, migration, and invasion in Fgfr1-expressing glioblastoma cell lines in culture, inhibited tumor growth in a cell line xenograft model, and inhibited growth and improved survival in an orthotopic xenograft model of glioblastoma (PMID: 37588207). 37588207