AZM475271

AZM475271 (M475271) is an orally active and selective Src kinase inhibitor. AZM475271 inhibits phosphorylation of c-Src kinase, Lck, c-yes (IC₅₀s = 0.01, 0.03, 0.08 μM, respectively). AZM475271 induces apoptosis. AZM475271 reduces tumor cell proliferation and migration in vitro and in vivo, and reduces microvessel density (MVD). AZM475271 inhibits tumor growth and metastasis. AZM475271 sensitizes tumor cells to the cytotoxic effects of Gemcitabine (HY-17026)^[1][2][3][4]. In Vitro:AZM475271 inhibits the proliferation of c-Src3T3 (transfected in fibroblast cells, 24 h, IC₅₀ = 0.53 μM) and A549 (72 h, IC₅₀ = 0.48 μM) cells^[1][2].
AZM475271 (1-20 μM, 48 h) shows no anti-proliferative effect on L3.6pl human pancreatic carcinoma cells in vitro below 15 μM, but induces cell death at 20 μM^[2].
AZM475271 (5 μM, 12 h) induces apoptosis and the effect can be enhanced by combination with Gemcitabine in L3.6pl cells^[2].
AZM475271 (0.1-5 μM, 4 h) inhibits L3.6pl cell migration^[2].
AZM475271 (1-10 μM, 4 h) demonstrates strong dose-dependent inhibition of Src tyrosine kinase activity in the L3.6pl cell line^[2].
AZM475271 effectively blocks TGF-β1-induced chemokinesis of Panc-1 cells and inhibits the high chemokinetic activity of Panc-1 cells with ectopic expression of a constitutively active ALK5T204D mutant. ^[3].
AZM475271 (10-100 µM, 24-72 h) inhibits SFK in prostate tissues and WPMY-1 cells, reduces α₁-adrenergic and neurogenic contraction of prostate strips^[4].
In Vivo:AZM475271(50 mg/kg; p.o.; once daily for 32 days) reduces tumor volume and the effect can be enhanced by combination with Gemcitabine (100 mg/kg; i.p.; twice weekly for 32 days) in athymic nude mice injected with L3.6pl cells^[2].
AZM475271 (50 mg/kg; p.o.; once) has biological effective plasma concentration with 24 hours in healthy nude mice ^[2].