2b7d
Factor VIIa Inhibitors: Chemical Optimization, Preclinical Pharmacokinetics, Pharmacodynamics, and Efficacy in a Baboon Thrombosis Model
OverviewOverview
Highly selective and potent factor VIIa-tissue factor (fVIIa.TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a baboon thrombosis model, and a pharmacodynamic concentration-response model was developed to describe the platelet deposition data. Results for heparin and enoxaparin (Lovenox) in the baboon model are also presented.
DiseaseDisease
Known disease associated with this structure: Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]
About this StructureAbout this Structure
2B7D is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model., Young WB, Mordenti J, Torkelson S, Shrader WD, Kolesnikov A, Rai R, Liu L, Hu H, Leahy EM, Green MJ, Sprengeler PA, Katz BA, Yu C, Janc JW, Elrod KC, Marzec UM, Hanson SR, Bioorg Med Chem Lett. 2006 Apr 1;16(7):2037-41. Epub 2006 Jan 18. PMID:16412633 Page seeded by OCA on Sat May 3 19:56:48 2008