2. Academic Validation
  3. Synthesis, in vitro, and in vivo evaluation of phosphate ester derivatives of combretastatin A-4

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

  • Bioorg Med Chem Lett. 2003 May 5;13(9):1505-8. doi: 10.1016/s0960-894x(03)00206-3.
Mallinath B Hadimani 1,  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
Affiliations

Affiliation

  • 1 Department of Chemistry & Biochemistry, Center for Drug Discovery, Baylor University, Waco, TX 76798-7348, USA.
PMID: 12699742 DOI: 10.1016/s0960-894x(03)00206-3
Abstract

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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