Document Report Card

ID: ALA1150765

Journal: J Med Chem

Title: Clavatadine A, a natural product with selective recognition and irreversible inhibition of factor XIa.

Authors: Buchanan MS, Carroll AR, Wessling D, Jobling M, Avery VM, Davis RA, Feng Y, Xue Y, Oster L, Fex T, Deinum J, Hooper JN, Quinn RJ.

Abstract: Bioassay-guided fractionation of a CH2Cl2/MeOH extract of the sponge Suberea clavata using the serine protease factor XIa to detect antithrombotic activity led to the isolation of the new marine natural products, clavatadines A and B. Clavatadines A and B inhibited factor XIa with IC50's of 1.3 and 27 microM, respectively. A crystal structure of protein-inhibitor (clavatadine A) complex was obtained and revealed interesting selective binding and irreversible inhibition of factor XIa. The cocrystal structure provides guidance for the design and synthesis of future factor XIa inhibitors as antithrombotic agents.

CiteXplore: 18510371

DOI: 10.1021/jm800314b