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Title: Inhibition of HIF-2.alpha. heterodimerization with HIF1.beta. (ARNT)

Abstract

Provided is a method of inhibiting heterodimerization of HIF-2.alpha. to HIF1.beta. (ARNT) comprising binding certain small molecules to the HIF-2.alpha. PAS-B domain cavity but not to HIF1.alpha. and inhibiting HIF-2.alpha. heterodimerization to HIF1.beta. (ARNT) but not inhibiting HIF1.alpha. heterodimerization to HIF1.beta. (ARNT). Those certain small molecules are also referenced synonymously as HIF2-HDI and HIF2.alpha. heterodimerization inhibitors and also simply as certain small molecules.

Inventors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1390247
Patent Number(s):
9,757,379
Application Number:
14/442,485
Assignee:
The Board of Regents of the University of Texas System ANL
DOE Contract Number:  
AC02-06CH11357
Resource Type:
Patent
Resource Relation:
Patent File Date: 2013 Nov 14
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Bruick, Richard K., Caldwell, Charles G., Frantz, Doug E., Gardner, Kevin H., MacMillan, John B., Scheuermann, Thomas H., and Tambar, Uttam K.. Inhibition of HIF-2.alpha. heterodimerization with HIF1.beta. (ARNT). United States: N. p., 2017. Web.
Bruick, Richard K., Caldwell, Charles G., Frantz, Doug E., Gardner, Kevin H., MacMillan, John B., Scheuermann, Thomas H., & Tambar, Uttam K.. Inhibition of HIF-2.alpha. heterodimerization with HIF1.beta. (ARNT). United States.
Bruick, Richard K., Caldwell, Charles G., Frantz, Doug E., Gardner, Kevin H., MacMillan, John B., Scheuermann, Thomas H., and Tambar, Uttam K.. Tue . "Inhibition of HIF-2.alpha. heterodimerization with HIF1.beta. (ARNT)". United States. doi:. https://www.osti.gov/servlets/purl/1390247.
@article{osti_1390247,
title = {Inhibition of HIF-2.alpha. heterodimerization with HIF1.beta. (ARNT)},
author = {Bruick, Richard K. and Caldwell, Charles G. and Frantz, Doug E. and Gardner, Kevin H. and MacMillan, John B. and Scheuermann, Thomas H. and Tambar, Uttam K.},
abstractNote = {Provided is a method of inhibiting heterodimerization of HIF-2.alpha. to HIF1.beta. (ARNT) comprising binding certain small molecules to the HIF-2.alpha. PAS-B domain cavity but not to HIF1.alpha. and inhibiting HIF-2.alpha. heterodimerization to HIF1.beta. (ARNT) but not inhibiting HIF1.alpha. heterodimerization to HIF1.beta. (ARNT). Those certain small molecules are also referenced synonymously as HIF2-HDI and HIF2.alpha. heterodimerization inhibitors and also simply as certain small molecules.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Sep 12 00:00:00 EDT 2017},
month = {Tue Sep 12 00:00:00 EDT 2017}
}

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Works referenced in this record:

Inhibition of Hypoxia Inducible Factor 1—Transcription Coactivator Interaction by a Hydrogen Bond Surrogate α-Helix
journal, January 2010

  • Henchey, Laura K.; Kushal, Swati; Dubey, Ramin
  • Journal of the American Chemical Society, Vol. 132, Issue 3, p. 941-943
  • DOI: 10.1021/ja9082864

Dimerization, DNA Binding, and Transactivation Properties of Hypoxia-inducible Factor 1
journal, July 1996

  • Jiang, Bing-Hua; Rue, Elizabeth; Wang, Guang L.
  • Journal of Biological Chemistry, Vol. 271, Issue 30, p. 17771-17778
  • DOI: 10.1074/jbc.271.30.17771

Principles of Ligand Binding within a Completely Buried Cavity in HIF2α PAS-B
journal, December 2009

  • Key, Jason; Scheuermann, Thomas H.; Anderson, Peter C.
  • Journal of the American Chemical Society, Vol. 131, Issue 48, p. 17647-17654
  • DOI: 10.1021/ja9073062

Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization
journal, October 2009

  • Lee, K.; Zhang, H.; Qian, D. Z.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 42, p. 17910-17915
  • DOI: 10.1073/pnas.0909353106

Inhibition of Hypoxia Inducible Factor-2 Transcription: Isolation of Active Modulators from Marine Sponges
journal, August 2012

  • McKee, Tawnya C.; Rabe, Daniel; Bokesch, Heidi R.
  • Journal of Natural Products, Vol. 75, Issue 9, p. 1632-1636
  • DOI: 10.1021/np300211x

Targeting the PAS-A Domain of HIF-1α for Development of Small Molecule Inhibitors of HIF-1
journal, July 2006

  • Park, Jung-Eun; Kong, Dehe; Fisher, Robert
  • Cell Cycle, Vol. 5, Issue 16, p. 1847-1853
  • DOI: 10.4161/cc.5.16.3019

Artificial ligand binding within the HIF2α PAS-B domain of the HIF2 transcription factor
journal, January 2009

  • Scheuermann, T. H.; Tomchick, D. R.; Machius, M.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 2, p. 450-455
  • DOI: 10.1073/pnas.0808092106

Hypoxia-Inducible Factors in Physiology and Medicine
journal, February 2012


Identification of Cys255 in HIF-1α as a novel site for development of covalent inhibitors of HIF-1α/ARNT PasB domain protein-protein interaction
journal, November 2012

  • Cardoso, Rosa; Love, Robert; Nilsson, Carol L.
  • Protein Science, Vol. 21, Issue 12, p. 1885-1896
  • DOI: 10.1002/pro.2172

Isoform-Selective and Stereoselective Inhibition of Hypoxia Inducible Factor-2
journal, July 2015

  • Scheuermann, Thomas H.; Stroud, Daniel; Sleet, Christopher E.
  • Journal of Medicinal Chemistry, Vol. 58, Issue 15, p. 5930-5941
  • DOI: 10.1021/acs.jmedchem.5b00529

Role of the Development Scientist in Compound Lead Selection and Optimization
journal, February 2000


Structure and Interactions of PAS Kinase N-Terminal PAS Domain
journal, October 2002