title: Purine-scaffold Hsp90 inhibitors.
abstract: Heat shock protein 90 (Hsp90) has emerged as an important target, the inhibition of which is aimed at a wide range of cell transformations that lead to malignancy. A clinical evaluation of 17-AAG, the first Hsp90 inhibitor to enter the clinic, revealed evidence of activity for the compound at a manageable level of toxicity. However, clinical results have also demonstrated the limitations of this drug. The identification of novel Hsp90 inhibitor classes with improved structural characteristics and better pharmacological profiles has therefore become a major focus of interest in the field of cancer therapeutics. This feature describes the purine-scaffold class of Hsp90 inhibitors, focusing on research efforts from the discovery stage to the clinical translation of such compounds.
authors.affiliation: Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. chiosisg@mskcc.org
authors.forename: Gabriela
authors.initials: G
authors.lastname: Chiosis
authors.forename: Hui
authors.initials: H
authors.lastname: Tao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D011687:Purines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011687:Purines