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PX-478 is a novel, orally active small molecule compound that acts as a highly potent and selective inhibitor of hypoxia-inducible factor 1-alpha (HIF-1α). It lowers HIF-1α protein levels and inhibits HIF-1 transactivation in both hypoxic and normoxic conditions across various cancer cell lines. PX-478 has demonstrated marked antitumor activity in preclinical models, including tumor regression and prolonged growth delay in multiple human cancer types such as lung, breast, prostate, colon, kidney, pancreas, and ovarian cancers. Its mechanism of action is independent of the tumor suppressor genes VHL and p53. The drug may also affect glucose uptake and metabolism by inhibiting glucose transporter 1 (Glut-1). In addition to its anticancer effects, PX-478 has shown potential benefits in metabolic disease models by improving pancreatic β cell function under high metabolic overload[2][7][6].
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