title: PU-H71: An improvement on nature's solutions to oncogenic Hsp90 addiction.
abstract: Despite recent advances in precision medicine, many molecular-based antineoplastic agents do not potentiate sustainable long term remissions, warranting the investigation of novel therapeutic strategies. Heat shock protein 90 (Hsp90) is a molecular chaperone that not only has oncogenic properties, but also has distinct expression profiles in malignant and normal cells, providing a rational strategy to attain preferential damage. Prior attempts to target Hsp90 with natural product-based compounds have been hampered by their associated off target toxicities, suggesting that novel, fully synthetic inhibitors may be required to achieve the specificity necessary for therapeutic efficacy. Therefore, this review highlights the antineoplastic potential of PU-H71 (8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine), a novel purine based analog that has shown efficacy in many preclinical models of malignancy, and is now under clinical examination. In addition, the review suggests potential concomitant therapeutic approaches that may be particularly beneficial to molecular-based, as well as traditional cytotoxic cancer chemotherapy.
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA; Department of Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, NY 10065, USA. Electronic address: mat2065@med.cornell.edu.
authors.forename: Matthew
authors.initials: M
authors.lastname: Trendowski
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D052117:Benzodioxoles / Q000627:therapeutic use*; D063646:Carcinogenesis / Q000187:drug effects* / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D011687:Purines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D052117:Benzodioxoles; D018841:HSP90 Heat-Shock Proteins; D011687:Purines; C526550:9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-
keywords: 17-AAG (17-N-allylamino-17-demethoxygeldanamycin/tanespimycin); 17-DMAG (17-desmethoxy-17-N,N-dimethylaminoethylaminogeldanamycin/alvespimycin); BIIB021 (6-chloro-9-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-9H-purin-2-amine); Cancer chemotherapy; Geldanamycin; Heat shock protein 90; IPI-504 (retaspimycin); PU-H71; PU-H71 (8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine); PU3 (9-butyl-8(3,4,5-trimethoxy-benzyl)-9H-purin-6-ylamine); Precision medicine; Radicicol; STA-9090 (ganetespib)