title: Heat shock protein 90 inhibitors as therapeutic agents.
abstract: The molecular chaperone heat shock protein 90 (HSP90) is essential for the folding stability, intracellular disposition and proteolytic turnover of many of the key regulators of cell growth, differentiation and survival. These essential functions are used by the cells during the oncogenesis process to allow the tumor transformation and facilitate the rapid somatic evolution. Inhibition of HSP90 would provide combinatorial blockade of a range of oncogenic pathways, antagonizing many of the hallmark traits of cancer. Several HSP90 inhibitors are currently under clinical trial investigation for the treatment of cancer. This review summarizes the current state and progress achieved in the development of HSP90 inhibitors targeting the N-terminal ATP pocket, C-terminal domain, different compartmentalized isoforms, and protein (cochaperones and/or client proteins)/HSP90 interactions. In the context of drug discovery, the most relevant patents which appeared recently in the literature are discussed as well.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Universita di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy. imgomez@unina.it
authors.forename: Isabel
authors.initials: I
authors.lastname: Gomez-Monterrey
authors.forename: Marina
authors.initials: M
authors.lastname: Sala
authors.forename: Simona
authors.initials: S
authors.lastname: Musella
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D055808:Drug Discovery / Q000331:legislation & jurisprudence / Q000379:methods; D004354:Drug Screening Assays, Antitumor / Q000379:methods / Q000639:trends; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins