Targeting heat-shock-protein 90 (Hsp90) by natural products

Geldanamycin, a show case in cancer therapy

authored by

Jana Franke, Simone Eichner, Carsten Zeilinger, Andreas Kirschning

Abstract

Covering: 2005 to 2013 In this review recent progress in the development of heat shock proteins (Hsp90) in oncogenesis is illuminated. Particular emphasis is put on inhibitors such as geldanamycin and analogues that serve as a natural product show case. Hsp90 has emerged as an important target in cancer therapy and/or against pathogenic cells which elicit abnormal Hsp patterns. Competition for ATP by geldanamycin and related compounds abrogate the chaperone function of Hsp90. In this context, this account pursues three topics in detail: a) Hsp90 and its biochemistry, b) Hsp90 and its role in oncogenesis and c) strategies to create compound libraries of structurally complex inhibitors like geldanamycin on which SAR studies and the development of drugs that are currently in different stages of clinical testing rely.

Organisation(s)

Department of Cell Physiology and Biophysics
Centre of Biomolecular Drug Research (BMWZ)
Institute of Organic Chemistry

Type

Review article

Journal

Natural Product Reports

Volume

30

Pages

1299-1323

No. of pages

25

ISSN

0265-0568

Publication date

10.2013

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Biochemistry, Drug Discovery, Organic Chemistry

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1039/c3np70012g (Access: Unknown)