IMR Press / FBL / Volume 17 / Issue 6 / DOI: 10.2741/4050

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Geldanamycin and its derivatives as Hsp90 inhibitors

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1 Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland. m.gorska@gumed.edu.pl
2 Department of Bioenergetics and Physiology of Exercise, Medical University of Gdansk, Gdansk, Poland
3 College of Health, Beauty Care and Education in Poznan, Faculty in Gdynia, Gdynia, Poland
4 Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy "Emerico Luna", University of Palermo, Palermo, Italy
5 Department of Oncology, Medical Oncology Unit, University of Palermo, Palermo, Italy

Academic Editor: Anna Czarnecka

Front. Biosci. (Landmark Ed) 2012, 17(6), 2269–2277; https://doi.org/10.2741/4050
Published: 1 June 2012
(This article belongs to the Special Issue Frontiers in molecular medicine)
Abstract

The Hsp90 molecule, one of the most abundant heat shock proteins in mammalian cells, maintains homeostasis and prevents stress-induced cellular damage. Hsp90 is expressed under normal conditions at a level of about 1-2 Percent of total proteins, while its expression increases 2-10 fold in cancer cells. The two main constitutively expressed isoforms of Hsp90 are known as Hsp90-alpha and Hsp90-beta, and their upregulation is associated with tumor progression, invasion and formation of metastases, as well as development of drug resistance. The Hsp90 is a key target for many newly established, potent anticancer agents containing Hsp90 N-terminal ATP binding inhibitors, such as geldanamycin, and its analogues 17AAG and 17DMAG. The therapeutic usage of geldanamycin has been limited due to its poor water solubility and severe hepatotoxicity. Therefore, its analogues, including 17AAG, 17DMAG, Tanespimycin and Retaspimycin hydrochloride, with improved pharmacokinetic profiles, have been developed.

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