Inhibition of Hypoxia Inducible Factor-2 Transcription: Isolation of Active Modulators from Marine Sponges

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Accepted Manuscript (AM)
Author(s)
McKee, Tawnya C.
Rabe, Daniel
Bokesch, Heidi R.
Grkovic, Tanja
Whitson, Emily L.
Diyabalanage, Thushara
Van Wyk, Albert W. W.
Marcum, Stephanie R.
Gardella, Roberta S.
Gustafson, Kirk R.
Marston Linehan, W.
McMahon, James B.
Bottaro, Donald P.
Griffith University Author(s)
Year published
2012
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Show full item recordAbstract
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-2a has been shown to have a distinct role in tumorigenesis. Our laboratories developed a cell-based screen to identify modulators of HIF-2a. 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 ...
View more >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-2a has been shown to have a distinct role in tumorigenesis. Our laboratories developed a cell-based screen to identify modulators of HIF-2a. 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-1a vs HIF-2a selectivity and the isolated compounds' effects on mRNA from several pathways regulated by HIF.
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View more >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-2a has been shown to have a distinct role in tumorigenesis. Our laboratories developed a cell-based screen to identify modulators of HIF-2a. 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-1a vs HIF-2a selectivity and the isolated compounds' effects on mRNA from several pathways regulated by HIF.
View less >
Journal Title
Journal of Natural Products
Volume
75
Issue
9
Copyright Statement
This document is the Accepted Manuscript version of a published work that appeared in final form in Journal of Natural Products, copyright 2012 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see 10.1021/np300211x
Subject
Natural Products Chemistry
Chemical Sciences
Biological Sciences
Medical and Health Sciences