Targeting Hsp90: small-molecule inhibitors and their clinical development.
The Hsp90 multichaperone complex has important roles in the development and progression of malignant transformation. Several small-molecule inhibitors of Hsp90 of diverse chemotypes have shown potent antitumor activity in a wide-range of malignancies, and are currently in clinical or late-stage preclinical investigation. This review intends to update the reader on advances made over the past two years in the clinical development of Hsp90 inhibitors in advanced cancers. It will refer to the two 17-AAG formulations, tanespimycin and IPI-504, and to synthetic small molecules, among which are the purine-scaffold Hsp90 inhibitor CNF2024/BIIB021, the isoxazole derivative VER-52296/NVP-AUY922, and the carbazol-4-one benzamide derivative SNX-5422, and will present our current knowledge on their clinical performance.
Taldone
Tony
T
Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Gozman
Alexander
A
Maharaj
Ronnie
R
Chiosis
Gabriela
G
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016227:Benzoquinones / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C001277:geldanamycin