PU-H71: An improvement on nature's solutions to oncogenic Hsp90 addiction Journal Article
| Author: | Trendowski, M. |
| Article Title: | PU-H71: An improvement on nature's solutions to oncogenic Hsp90 addiction |
| Abstract: | 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. © 2015 The Authors. |
| Keywords: | cancer chemotherapy; unclassified drug; drug efficacy; liver cell carcinoma; drug targeting; outcome assessment; antineoplastic agent; protein function; multiple myeloma; drug potency; drug structure; structure activity relation; ewing sarcoma; cancer inhibition; hematologic malignancy; breast carcinoma; drug response; lymphoma; heat shock protein 90; lung carcinoma; clinical effectiveness; drug cytotoxicity; protein structure; drug determination; protein determination; epithelium tumor; myeloproliferative neoplasm; thymic epithelial tumors; thymic epithelial tumor; pu-h71; human; priority journal; article; precision medicine; ic50; 8 [(6 iodo 1,3 benzodioxol 5 yl)sulfanyl] 9 [3 (propan 2 ylamino)propyl]purin 6 amine |
| Journal Title: | Pharmacological Research |
| Volume: | 99 |
| ISSN: | 1043-6618 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2015-09-01 |
| Start Page: | 202 |
| End Page: | 216 |
| Language: | English |
| DOI: | 10.1016/j.phrs.2015.06.007 |
| PROVIDER: | scopus |
| PUBMED: | 26117427 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
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