Reference Detail

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.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Genes & diseases	11	1	2024 Jan	479-494	Genes Dis

URL

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