| Autor: |
Sushanta K. Banerjee, Peter J. Van Veldhuizen, Emma Borrego-Diaz, Douglas Burns, Saheli Jha, Snigdha Banerjee, Amlan Das, Inamul Haque, Mehmet Tanol, Roger A. Rajewski, Suman Kambhampati |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1535-7163.c.6535956 |
| Popis: |
2-Methoxyestradiol (2-ME2) is an endogenous metabolite of estradiol. In preclinical models, 2-ME2 is effective against different types of tumors. Unfortunately, only low systemic concentrations of 2-ME2 can be achieved following oral administration, even after very high doses are administered to patients. In an effort to solve this problem, we have now synthesized and tested a new prodrug of 2-ME2 that is water-soluble due to a bioreversible hydrophilic group added at the 3-position and that more effectively resists metabolic inactivation due to an ester moiety added to mask the 17-position alcohol. We are reporting here for the first time that this double prodrug of 2-ME2 is effective as an antiproliferative and anticancer agent for both in vitro and in vivo studies against Barrett esophageal adenocarcinoma (BEAC) and provided greater potency than 2-ME2 in inhibiting the growth of BEAC xenografts. Finally, studies indicate that, like 2-ME2, the 2-ME2-PD1 exhibits anticancer effect through possible disruption of microtubule network. Mol Cancer Ther; 12(3); 255–63. ©2012 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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