Inhibition of hypoxia inducible factor-2 transcription: isolation of active modulators from marine sponges

J Nat Prod. 2012 Sep 28;75(9):1632-6. doi: 10.1021/np300211x. Epub 2012 Aug 28.


Renal or kidney cancer accounts for about 3% of all cancer cases reported each year in the U.S. Molecular signatures that define the cancer, such as the loss of functional VHL, are found in both sporadic and familial cases of cancer. In clear cell renal cancer, the transcription factor HIF-2α has been shown to have a distinct role in tumorigenesis. Our laboratories developed a cell-based screen to identify modulators of HIF-2α. Screening of the NCI's Natural Product Extract Repository resulted in the identification of 10 sponge extracts, from which 12 compounds were isolated. The biological evaluation of these compounds will be discussed including evaluation of HIF-1α vs HIF-2α selectivity and the isolated compounds' effects on mRNA from several pathways regulated by HIF.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Biological Products / chemistry
  • Biological Products / isolation & purification*
  • Biological Products / pharmacology*
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Marine Biology
  • Molecular Structure
  • Porifera / chemistry*
  • RNA, Messenger / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • Biological Products
  • RNA, Messenger
  • endothelial PAS domain-containing protein 1