Small-molecule inhibitor: DPC423

Name

History: The background to the development of DPC423 is described by Quan & Wexler (2001) and Pinto et al. (2001. DPC-423 was discovered as a result of optimisation of DuPont"s compound SN-429, including replacement of the benzamidine moiety with a less basic benzylamine (Taglialatela, 2002).
Peptidases inhibited: DPC423 is a highly-selective inhibitor of factor Xa.
Mechanism: Inhibition is reversible, K_i 0.15 nM for factor Xa. This specific inhibition can be contrasted with K_i values of 60 nM for trypsin and 600 nM for thrombin (Quan & Wexler, 2001).
Pharmaceutical relevance: Thrombosis is a major cause of mortality in the industrialized world, so the control of blood coagulation has become a major target for new therapeutic agents. One attractive approach is the inhibition of factor Xa, the enzyme directly responsible for thrombin generation, and DPC423 is such an inhibitor..

Structure
Chemical/biochemical name: 1-[3-(aminomethyl)phenyl]-N-[3-fluoro-2'- (methylsulfonyl)-[1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide