Bioorganic and Medicinal Chemistry Letters p. 1505 - 1508 (2003)
Update date:2022-08-02
Topics: Data Analysis In Vitro Evaluation In Vivo Evaluation Pharmacokinetics and Pharmacodynamics Publication and Further Development Bioavailability and Formulation Toxicology and Safety Assessment
Hadimani, Mallinath B.
Hua, Jianyi
Jonklaas, M. Devan
Kessler, Raymond J.
Sheng, Yezhou
Olivares, Adrian
Tanpure, Rajendra P.
Weiser, Aimee
Zhang, Jianxing
Edvardsen, Klaus
Kane, Robert R.
Pinney, Kevin G.
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 (IC50=1-2 μM), 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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