A heat shock protein 90 inhibitor that modulates the immunophilins and regulates hormone receptors without inducing the heat shock response

Bioorganic & Medicinal Chemistry Letters
Jeanette R McConnellShelli R McAlpine

Abstract

When a cell encounters external stressors, such as lack of nutrients, elevated temperatures, changes in pH or other stressful environments, a key set of evolutionarily conserved proteins, the heat shock proteins (hsps), become overexpressed. Hsps are classified into six major families with the hsp90 family being the best understood; an increase in cell stress leads to increased levels of hsp90, which leads to cellular protection. A hallmark of hsp90 inhibitors is that they induce a cell rescue mechanism, the heat shock response. We define the unique molecular profile of a compound (SM145) that regulates hormone receptor protein levels through hsp90 inhibition without inducing the heat shock response. Modulation of the binding event between heat shock protein 90 and the immunophilins/homologs using SM145, leads to a decrease in hormone receptor protein levels. Unlike N-terminal hsp90 inhibitors, this hsp90 inhibitor does not induce a heat shock response. This work is proof of principle that controlling hormone receptor expression can occur by inhibiting hsp90 without inducing pro-survival protein heat shock protein 70 (hsp70) or other proteins associated with the heat shock response. Innovatively, we show that blocking the heat ...Continue Reading

References

Apr 29, 2000·Electrophoresis·C SartoP Mocarelli
Oct 6, 2000·Journal of the National Cancer Institute·C Jolly, R I Morimoto
Mar 9, 2002·Science·F Ulrich Hartl, Manajit Hayer-Hartl
Apr 3, 2002·Trends in Molecular Medicine·Len Neckers
Oct 8, 2003·Current Cancer Drug Targets·Luke WhitesellRyan Falsey
Dec 10, 2003·Oncogene·Shinichi TakayamaSachiko Homma
Oct 16, 2008·Anti-cancer Agents in Medicinal Chemistry·M K Hadden, B S J Blagg
Dec 17, 2009·Biochimica Et Biophysica Acta·Pablo C Echeverria, Didier Picard
Aug 24, 2010·ACS Medicinal Chemistry Letters·Robert C VaskoShelli R McAlpine
Sep 6, 2011·Trends in Endocrinology and Metabolism : TEM·Cheryl L StorerMarc B Cox
Sep 29, 2011·ACS Chemical Biology·Veronica C ArdiShelli R McAlpine

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Citations

Nov 5, 2014·Future Medicinal Chemistry·Jessica A HallBrian S J Blagg
Dec 11, 2013·Organic & Biomolecular Chemistry·Hendra WahyudiShelli R McAlpine
Feb 17, 2015·Future Medicinal Chemistry·Yao Wang, Shelli R McAlpine
Feb 1, 2017·ChemMedChem·Yao WangShelli R McAlpine
Nov 4, 2015·Chemical Communications : Chem Comm·L K BucktonS R McAlpine
Feb 26, 2015·Organic & Biomolecular Chemistry·Y Wang, S R McAlpine
Dec 6, 2017·International Journal of Molecular Sciences·Gabriel R FriesTheo Rein
Oct 22, 2014·Chemical Communications : Chem Comm·Y Wang, S R McAlpine
Nov 20, 2016·Chemistry : a European Journal·Yen Chin KoayShelli R McAlpine
Jan 26, 2016·ChemMedChem·Yen Chin KoayShelli R McAlpine
Sep 3, 2020·Chemistry : a European Journal·Laura K BucktonShelli R McAlpine
Sep 15, 2019·Bioorganic & Medicinal Chemistry·David Bickel, Holger Gohlke
Feb 21, 2021·Bioorganic & Medicinal Chemistry Letters·Oi Wei MakIvanhoe K H Leung
Apr 27, 2021·RSC Medicinal Chemistry·Jeanette R McConnellShelli R McAlpine
Jul 23, 2014·ACS Medicinal Chemistry Letters·Yen Chin KoayShelli R McAlpine

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