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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. 2017. "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 = 2017,
month = 9
}

Patent:

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  • A method for increasing or monitoring apoptosis in tumor cells by the co-administration of ionizing radiation and an anti-integrin antibody. Increasing apoptosis reduces tumor growth in vivo and in a cell culture model. The antibody is directed against the beta-1 integrin subunit and is inhibitory of beta-1 integrin signaling. Other molecules having an inhibitory effect on beta-1 integrin, either in signaling or in binding to its cognate extracellular receptors may also be used. The present method is particularly of interest in treatment of tumor cells associated with breast cancer, wherein radiation is currently used alone. The present method further contemplatesmore » a monoclonal antibody suitable for human administration that may further comprise a radioisotope attached thereto.« less
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