Targeting heat-shock-protein 90 (Hsp90) by natural products: geldanamycin, a show case in cancer therapy.
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.
Institut für Organische Chemie und Zentrum für Biomolekulare Wirkstoffchemie (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, D-30167 Hannover, Germany. andreas.kirschning@oci.uni-hannover.de.
Jana
J
Franke
Simone
S
Eichner
Carsten
C
Zeilinger
Andreas
A
Kirschning
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D016227:Benzoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D015394:Molecular Structure
D000970:Antineoplastic Agents; D016227:Benzoquinones; D001688:Biological Products; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C001277:geldanamycin