BioCentury
ARTICLE | Product R&D

Pocketing cancer

How UT Southwestern academics found way to target HIF2A, Peloton got antagonist to clinic

June 18, 2015 7:00 AM UTC

Although the hypoxic response pathway has long been of interest in cancer, directly blocking hypoxia-inducible factors (HIFs) has been a problem because of the lack of an obvious or easily accessible binding site. Using a series of iterative structure-activity studies, a group at UT Southwestern uncovered a hidden binding pocket within HIF2A and developed a set of small molecule antagonists that bind the site and block transcription.

The group, led by Richard Bruick - a former post-doc of Steven McKnight - licensed the molecules to Peloton Therapeutics Inc., which disclosed the first preclinical data for its HIF2A program at the American Association for Cancer Research (AACR) meeting in April. McKnight is chairman of the biochemistry department at University of Texas Southwestern Medical Center and co-founder of Peloton, which began Phase I trials on its oral HIF2A antagonist PT2385 in advanced clear cell renal cell carcinoma (ccRCC) in December. The company expects the first clinical data next year. ...