PU-H71: An improvement on nature's solutions to oncogenic Hsp90 addiction

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• 作者：Matthew Trendowski^a ; ^b ; ^{mat2065@med.cornell.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Geldanamycin ; Radicicol ; 17-AAG (17-N-allylamino-17-demethoxygeldanamycin/tanespimycin) ; 17-DMAG (17-desmethoxy-17-N ; N-dimethylaminoethylaminogeldanamycin/alvespimycin) ; IPI-504 (retaspimycin) ; STA-9090 (ganetespib) ; PU3 (9-butyl-8(3 ; 4 ; 5-trimethoxy-benzyl)-9H-purin-6-ylamine) ; BIIB021 (6-chloro-9-((4-methoxy-3 ; 5-dimethylpyridin-2-yl)methyl)-9H-purin-2-amine) ; PU-H71 (8-[(6-iodo-1 ; 3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine)
• 刊名：Pharmacological Research
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：99
• 期：Complete
• 页码：202-216
• 全文大小：1714 K

文摘

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.