18378-26-2Relevant academic research and scientific papers
INHIBITION OF HIF-2α HETERODIMERIZATION WITH HIF1β (ARNT)
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Paragraph 096, (2014/06/11)
Provided is a method of inhibiting heterodimerization of HIF-2α to HIF1β (ARNT) comprising binding certain small molecules to the HIF-2α PAS-B domain cavity but not to HIF1α and inhibiting HIF-2α heterodimerization to HIF1β (ARNT) but not inhibiting HIF1α
Development of inhibitors of the PAS-B domain of the HIF-2α transcription factor
Rogers, Jamie L.,Bayeh, Liela,Scheuermann, Thomas H.,Longgood, Jamie,Key, Jason,Naidoo, Jacinth,Melito, Lisa,Shokri, Cameron,Frantz, Doug E.,Bruick, Richard K.,Gardner, Kevin H.,MacMillan, John B.,Tambar, Uttam K.
supporting information, p. 1739 - 1747 (2013/03/29)
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-2α-ARNT heterodimerization by binding an internal cavity of the HIF-2α 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-2α-ARNT PAS-B interaction. These results may serve as a foundation for discovering therapeutic agents that function by a novel mode of action.
