Small molecule inhibitors of plasma kallikrein

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 7, 2006, Pages 2034-2036

  Young, Wendy B ^a   Rai, Roopa ^a   Shrader, William D ^a   Burgess Henry, Jana ^a   Hu, Huiyong ^a   Elrod, Kyle C ^a   Sprengeler, Paul A ^a   Katz, Bradley A ^a   Sukbuntherng, Juthamas ^a   Mordenti, Joyce ^a  

^a CELERA   (United States)

Author keywords

Coagulation; Fibrinolysis; Kinin generation; p kallikrein; Plasma kallikrein; Serine protease; Small molecule inhibitor

Indexed keywords

BENZIMIDAZOLE DERIVATIVE; KALLIKREIN; KALLIKREIN INHIBITOR;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BINDING KINETICS; CONTROLLED STUDY; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; ENZYME BLOOD LEVEL; INHIBITION KINETICS; MALE; MEAN RESIDENCE TIME; MOLECULE; NONHUMAN; PLASMA CLEARANCE; RAT; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

KALLIKREINS; SERINE PROTEINASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

ANIMALIA;

EID: 33144472151     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.12.060     Document Type: Article

References (22)

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18. 2. Trypsin (Athens Research Institute) was incubated at 10 nM with variable concentrations of inhibitor in 50 mM Tris (pH 7.4), 150 mM NaCl, 1.5 mM EDTA, 0.05% Tween 20, and 10% DMSO. The reaction was initiated with substrate, Tosyl-Gly-Pro-Lys-pNA (Centerchem), supplied at the Km (25 μM). Plasma Kallikrein (Athens Research Institute) was incubated at 540 pM with variable concentrations of inhibitor in 50 mM Tris (pH 7.4), 150 mM NaCl, 500 μM EDTA, 0.05% Tween 20, and 10% DMSO. The reaction was initiated with substrate, Pro-Phe-Arg-AMC (Bachem), supplied at the Km (350 μM)
19. The PDB access code for the X-ray coordinates is 2ANW.
20. The PDB access code for the X-ray coordinates is 2ANY.
21. Tang, J.; Yu, C.; Williams, S.R.; Springman, E.; Jeffreys, D.; Sprengeler, P.; Estevez, A.; Sampang, J.; Shrader, W.; Spencer, J.; Young, W.; McGrath, M.; Katz, B. J. Mol. Biol. in press.
22. Plasma concentrations of 11 were assayed by LC/MS/MS (LOQ = 0.00457 μM). Pharmacokinetic data were analyzed by WinNonlin-Pro (Pharsight Corp.), using a three-compartment model.