compound introduction
Information PT2399 PT2399 is a potent and orally available antagonist of HIF-2 that selectively disrupts the heterodimerization of HIF-2α with HIF-1β . Targets HIF-2α ; HIF-1β In vivo PT2399 dissociates HIF-2 (an obligatory heterodimer [HIF-2α/HIF-1β])14 in human Clear cell Renal Cell Carcinoma (ccRCC) suppressing tumorigenesis in 56% (10/18) lines. PT2399 has greater activity than sunitinib, is active in sunitinib-progressing tumors, and is better tolerated. Illustrating drug specificity, gene expression is largely unaffected by PT2399 in resistant tumors. Sensitive tumors exhibits a distinguishing gene expression signature, and generally higher HIF-2α levels. Prolonged PT2399 treatment leads to resistance.
