PX-478 | HY-10231

PX-478 is an orally active HIF-1α inhibitor with potent antitumor activities. PX-478 can cross the blood-brain barrier[1][2].

IC50 & Target :

HIF-1α[1]

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[1].

In Vivo:

PX-478 is administered to mice with congenital HO (Nfatc1-Cre/caACVR1fl/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)[2].

Molecular weight:

394.12

Formula:

C₁₃H₂₀Cl₄N₂O₃

SMILES:

[O-][N+](CCCl)(CCCl)C(C=C1)=CC=C1C[C@H](N)C(O)=O.Cl.Cl

Storage:

-20°C, stored under nitrogen, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)