FGFR-IN-13 (compound III-30) is an irreversible covalent fibroblast growth factor receptor (FGFR) inhibitor. FGFR-IN-13 regulates endogenous FGFR1(IC50=0.20±0.02 nM) and FGFR4(IC50=0.40±0.03 nM) mediated signaling pathways by inhibiting the expression of key proteins. FGFR-IN-13 inhibits total-PARP and Bcl-2 protein expressions, and promote Cleaved-PARP and Bax protein expressions in a dose-dependent manner. FGFR-IN-13 has significant antitumor activity and oral activity[1].
in vivo
FGFR-IN-13 (10 and 30 mg/kg, po; everyday for 21 days) inhibits tumor growth in a dose-dependent manne. FGFR-IN-13 has a favorable safety profile and is effective in inhibiting tumor growth at safe doses in MDA-MB-231 xenograft tumor mouse mode[1].
Animal Model:
MDA-MB-231 xenograft tumor mouse model[1]
Dosage:
10 and 30 mg/kg
Administration:
Oral gavage (p.o.)
Result:
Did not cause significant weight loss.
Achieved tumor growth inhibition (TGI) of 64.21% at high doses (30 mg/kg).
Achieved tumor growth inhibition (TGI) of 40.22% at low doses (10 mg/kg).
References
[1] Wang Y, et al. Discovery of N-(4-((6-(3, 5-Dimethoxyphenyl)-9H-Purine Derivatives as Irreversible Covalent FGFR Inhibitors[J]. European Journal of Medicinal Chemistry, 2024: 116415. DOI:10.1016/j.ejmech.2024.116415
