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ID: ALA1268832

Journal: Bioorg Med Chem Lett

Title: Discovery of a potent tubulin polymerization inhibitor: synthesis and evaluation of water-soluble prodrugs of benzophenone analog.

Authors: Lee J, Bae S, Lee SH, Choi H, Kim YH, Kim SJ, Park GT, Moon SK, Kim DH, Lee S, Ahn SK, Choi NS, Lee KJ.

Abstract: Prodrugs have proven to be very useful in enhancing aqueous solubility of sparingly water-soluble drugs, thereby increasing in vivo efficacy without a need of special excipients. In vitro and in vivo evaluations of a number of amino acid prodrugs of 1, a previously identified potent tubulin polymerization inhibitor and cytotoxic against various cancer cell lines led to the discovery of 3·HCl (l-valine attached) which is highly efficacious in mouse xenografts bearing human cancer. Pharmacokinetic analysis in rats revealed that compound 1 was released immediately upon administration of 3·HCl intravenously, with rapid clearance of 3·HCl indicating the effective cleavage of prodrug. Compound 3·HCl (CKD-516) has now been progressed to phase 1 clinical trial.

CiteXplore: 20850313

DOI: 10.1016/j.bmcl.2010.05.060