title: Alternative approaches to Hsp90 modulation for the treatment of cancer.
abstract: Hsp90 is responsible for the conformational maturation of newly synthesized polypeptides (client proteins) and the re-maturation of denatured proteins via the Hsp90 chaperone cycle. Inhibition of the Hsp90 N-terminus has emerged as a clinically relevant strategy for anticancer chemotherapeutics due to the involvement of clients in a variety of oncogenic pathways. Several immunophilins, co-chaperones and partner proteins are also necessary for Hsp90 chaperoning activity. Alternative strategies to inhibit Hsp90 function include disruption of the C-terminal dimerization domain and the Hsp90 heteroprotein complex. C-terminal inhibitors and Hsp90 co-chaperone disruptors prevent cancer cell proliferation similar to N-terminal inhibitors and destabilize client proteins without induction of heat shock proteins. Herein, current Hsp90 inhibitors, the chaperone cycle, and regulation of this cycle will be discussed.
authors.affiliation: Department of Medicinal Chemistry, The University Of Kansas, 1251 Wescoe Hall Drive, 4070 Malott Hall, Lawrence, KS 66045, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hall
authors.forename: Leah K
authors.initials: LK
authors.lastname: Forsberg
authors.forename: Brian S J
authors.initials: BS
authors.lastname: Blagg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D055808:Drug Discovery; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009675:Novobiocin / Q000031:analogs & derivatives / Q000494:pharmacology; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D012838:Silymarin; D009675:Novobiocin; D000077385:Silybin; D002392:Catechin; C045651:epigallocatechin gallate