Publication Date:
2005-11-16
Description:
Based on previous studies showing the efficacy of FactorIXa (FIXa) blockade using an active site-blocked form of this coagulation enzyme, we speculated that partial inhibition of the intrinsic coagulation pathway would offer a novel approach to attenuate intravascular clot formation without promoting untoward bleeding. Here we describe the anticoagulant activity of TTP889, a small molecule partial inhibitor of FIXa activity. TTP889 is orally absorbed with a PK profile that is conducive to once daily dosing. It is selective for FIXa in that it shows little to no activity against several other proteases in the clotting cascade including FXa, FXIa, FXIIa or FVIIa in a unique clotting assay. In vivo, TTP889 inhibited fibrin deposition in a rat arteriovenous (A/V) shunt model. In this model, vehicle treated rats had 104mg ± 43 of fibrin deposited on a silk thread after a 15 minute shunt while TTP889 treated rats had significantly less fibrin deposited (39mg ± 18 p=
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
Permalink