Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 56, Issue 4, Pages 1739-1747Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm301847z
Keywords
-
Categories
Funding
- NIH [P01 CA095471, CPRIT RP100846, 5P30 CA142543]
- Welch Foundation [I-1689, I-1568]
- Burroughs Wellcome Fund
- National Center for Research Resources, National Institutes of Health [C06 RR 15437-01]
- U.S. Department of Energy, Office of Biological and Environmental Research [DE-AC02-06CH11357]
Ask authors/readers for more resources
Hypoxia inducible factors (HIFs) are heterodimeric transcription factors induced in a variety of pathophysiological settings, including cancer. We describe the first detailed structure-activity relationship study of small molecules designed to inhibit HIF-2 alpha-ARNT heterodimerization by binding an internal cavity of the HIF-2 alpha PAS-B domain. Through a series of biophysical characterizations of inhibitor-protein interactions (NMR and X-ray crystallography), we have established the structural requirements for artificial inhibitors of the HIF-2 alpha-ARNT PAS-B interaction. These results may serve as a foundation for discovering therapeutic agents that function by a novel mode of action.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available