(S)-4-(2-氨基-2-羧乙基)-N,N-双(2-氯乙基)环己-1,3-二苯胺氧化物二盐酸盐

PX-478 2HCl是一种具有口服活性的选择性hypoxia-inducible factor-1α (HIF-1α)抑制剂。Phase 1。 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. PX-478 also enhances the radiosensitivity of prostate carcinoma PC3 cells. 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. In high-fat-diet mice, PX-478 causes reduced fibrosis and fewer inflammatory infiltrates in their adipose tissues. PX-478 2HCl 是一种具有口服活性的选择性hypoxia-inducible factor-1α (HIF-1α)抑制剂。PX-478 2HCl可诱导凋亡并具有抗肿瘤的活性。Phase 1。

Target	Value
HIF-1α

PX-478降低缺氧和常氧环境下各种细胞系中HIF-1α蛋白水平和HIF-1反式激活，并且对蛋白质的翻译具有更显著的作用，比如缺氧环境下的 HIF-1α。 PX-478也能够增强前列腺癌PC3细胞的放射敏感性。

在HT-29人结肠癌异种移植物中，PX-478抑制HIF-1α的水平，并抑制HIF-1靶点基因的表达，包括血管内皮生长因子和葡萄糖转运体-1。此外，PX-478 (100 或120 mg/kg i.p.)也表现出抗肿瘤活性，包括治愈几种建立的与HIF-1α水平相关的人肿瘤异种移植物。在高脂饮食小鼠体内，PX-478减少它们脂肪组织中的纤维化病变和炎症浸润。