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PX-478

CAS No. : 685898-44-6

MCE 国际站：PX-478

产品活性：PX-478 是一种具有口服活性的 HIF-1α 抑制剂，并具有抗癌活性。PX-478 可穿透血脑屏障。

研究领域：Metabolic Enzyme/Protease  |  Autophagy

作用靶点：HIF/HIF Prolyl-Hydroxylase  |  Autophagy

In Vitro: PC3 and DU 145 cells express HIF-1α protein are treated with PX-478 for 20 hr under normoxia. PC3 cells are more sensitive to PX-478 as compared with DU 145 cells. Densitometric analysis shows that the IC₅₀ for HIF-1α inhibition for PC3 cells under normoxic condition is 20-25 μM, whereas the IC₅₀ for HIF-1α inhibition for the DU 145 cells is 40-50 μM. PC3 and DU 145 cells are treated with different concentrations of PX-478 (10, 20, 30, 40, 50, and 60 μM) for 18-20 hr under normoxia or hypoxia. Under normoxia, PC3 cells are more sensitive to PX-478 than DU 145 cells. IC₅₀ for clonogenic survival (n=3) is 17 μM for PC3 cells and 35 μM for DU 145 cells. When cells are treated with the drug under hypoxic condition for 18 hr, the IC₅₀ is 16 μM for PC3 cells and 22 μM for DU 145 cells. Thus DU 145 cells are more sensitive to PX-478 under hypoxic condition.

In Vivo: PX-478 is administered to mice with congenital heart disease (Nfatc1-Cre/caACVR1^fl/fl) every other day starting from birth for 2 wk. Treated mice have significantly less ectopic bone at the ankle joints compared with mutant mice treated with vehicle (6.8 mm³ vs. 2.2 mm³, P<0.01).

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