Hypoxia inducible factors (HIFs), including HIF-1α and HIF-2α, are transcription factors that mediate cellular responses to diminished oxygen supply. These proteins become stabilized under hypoxia (low oxygen) and subsequently activate the expression of genes to facilitate cell survival and proliferation. HIF proteins are activated in many types of cancers and have been implicated in cancer initiation, progression, and metastasis. The role of HIF-2α is particularly important in clear cell renal cell carcinoma (ccRCC). In the majority of ccRCC tumors, the tumor suppressor von Hippel-Lindau protein (pVHL) that targets HIF-2α for degradation is inactivated, leading to the accumulation of HIF-2α and the transcription of genes that drive kidney cancer tumorigenesis. PT2385 is a selective, orally active agent that blocks HIF-2α with potent anti-cancer activity in preclinical models of ccRCC. PT2385 is currently under evaluation in a Phase 1 clinical trial for the treatment of advanced ccRCC.
|PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma||Open/Recruiting||NCT03108066||PT2385 VHL Trial|
|A Trial of PT2977 Tablets In Patients With Advanced Solid Tumors||Open/Recruiting||NCT02974738||PT2977 Trial|
|PT2385-102 Food Effect Study of PT2385 in Healthy Volunteers||Completed||NCT02553356||PT2385-102 Trial|
|A Phase 1, Dose-Escalation Trial of PT2385 Tablets In Patients With Advanced Clear Cell Renal Cell Carcinoma||Open/Recruiting||NCT02293980||RCC Trial|