Small-molecule inhibitor: ZK-807834

Name

History: Phillips et al. (1998) described ZK-807834 as a potent inhibitor of coagulation factor Xa.
Peptidases inhibited: Factor Xa is inhibited with extreme selectivity (Adler et al., 2000).
Mechanism: Inhibition is reversible, with K_i 0.11 nM. The mode of binding to the enzyme is illustrated by the crystal structure (Adler et al., 2000).
Pharmaceutical relevance: The control of blood coagulation is of very great medical importance. ZK-807834 is a selective inhibitor of factor Xa, and as such, it inhibits the conversion of prothrombin to thrombin by factor Xa, and thus inhibits the conversion of fibrinogen to fibrin. Thrombin itself not only converts fibinogen to fibrin, but has a variety of other activities, and there are reasons to think that the inhibition of coagulation by inhibition of factor Xa may be preferable to inhibition of thrombin itself under some conditions (Nicolini et al., 1996; Komoriya et al., 2004). ZK-807834 is considered a promising agent for doing this.

CID at PubChem: 6433096
Structure
Chemical/biochemical name: 2-[[2-[[3-(diaminomethylidene)-6-oxo-1-cyclohexa-1,4-dienyl]oxy]-3,5-difluoro-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyridin-4-yl]methylamino]acetic acid
Formula weight: 526