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Synthesis, in vitro, and in vivo evaluation of phosphate ester derivatives of combretastatin A-4. | LitMetric
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Synthesis, in vitro, and in vivo evaluation of phosphate ester derivatives of combretastatin A-4.

Mallinath B Hadimani Jianyi Hua M Devan Jonklaas Raymond J Kessler Yezhou Sheng Adrian Olivares Rajendra P Tanpure Aimee Weiser Jianxing Zhang Klaus Edvardsen Robert R Kane Kevin G Pinney

Bioorg Med Chem Lett

Department of Chemistry & Biochemistry, Center for Drug Discovery, Baylor University, Waco, TX 76798-7348, USA.

Published: May 2003

Combretastatin A-4 disodiumphosphate (CA4P), a prodrug formulation of the natural product combretastatin A-4 (CA4), is currently in clinical investigation for the treatment of cancer. In vivo, CA4P is rapidly enzymatically converted to CA4, a potent inhibitor of tubulin polymerization (IC(50)=1-2 microM), and rapidly causes bloodflow shutdown in tumor tissues. A variety of alkyl and aryl di- and triesters of CA4P have been synthesized and evaluated as potential CA4 prodrugs and/or stable CA4P analogues.

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http://dx.doi.org/10.1016/s0960-894x(03)00206-3DOI Listing

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