PX-478 是一种具有口服活性的选择性缺氧诱导因子 1α (HIF-1α) 抑制剂。它可穿透血脑屏障，具有抗癌活性。

PX-478 2HCl is an orally active, and selective inhibitor of hypoxia-inducible factor-1α (HIF-1α).

PX-478 lowers HIF-1α protein levels and HIF-1 transactivation in hypoxia and in normoxia in a variety of cancer cell lines, but has a more pronounced effect on translation of proteins, such as HIF-1α in hypoxia. [2] PX-478 also enhances the radiosensitivity of prostate carcinoma PC3 cells. [3]

In HT-29 human colon cancer xenografts, PX-478 suppresses HIF-1alpha levels and inhibits the expression of HIF-1 target genes including vascular endothelial growth factor and the glucose transporter-1. In addition, PX-478 (100 or 120 mg/kg i.p.) also shows antitumor activity including cures against several established human tumor xenografts that is related to the levels of HIF-1α. [1] In high-fat-diet mice, PX-478 causes reduced fibrosis and fewer inflammatory infiltrates in their adipose tissues. [4]

PX-478 is prepared as a 10 mM stock in distilled water and used immediately[1]. To determine the effect of PX-478 in combination with radiation, cells are treated with PX-478 for 24 hr under normoxic condition, irradiated and plated after 1 hr. Colonies are stained with crystal violet after 12 days and the colonies of >50 cells are counted. For combination treatments, net survival is calculated by correcting the toxicity of PX-478 alone. Enhancement factor (EF) is calculated by dividing the dose of radiation required to reduce plating efficiency to 10% when cells are treated with radiation alone by the dose of radiation required to reduce plating efficiency to 10% when cells are treated with PX-478 and radiation[1].

685898-44-6

C13H20Cl4N2O3

394.11

PX-478 2HCl

DMSO:197.9 mM
H2O:88.81mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years