2viw
From Proteopedia
|
FRAGMENT-BASED DISCOVERY OF MEXILETINE DERIVATIVES AS ORALLY BIOAVAILABLE INHIBITORS OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR
Overview
Fragment-based lead discovery has been applied to urokinase-type, plasminogen activator (uPA). The ( R)-enantiomer of the orally active drug, mexiletine 5 (a fragment hit from X-ray crystallographic screening) was, the chemical starting point. Structure-aided design led to elaborated, inhibitors that retained the key interactions of ( R)- 5 while gaining, extra potency by simultaneously occupying neighboring regions of the, active site. Subsequent optimization led to 15, a potent, selective, and, orally bioavailable inhibitor of uPA.
About this Structure
2VIW is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as U-plasminogen activator, with EC number 3.4.21.73 Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Fragment-based discovery of mexiletine derivatives as orally bioavailable inhibitors of urokinase-type plasminogen activator., Frederickson M, Callaghan O, Chessari G, Congreve M, Cowan SR, Matthews JE, McMenamin R, Smith DM, Vinkovic M, Wallis NG, J Med Chem. 2008 Jan 24;51(2):183-6. Epub 2007 Dec 29. PMID:18163548
Page seeded by OCA on Thu Jan 31 11:01:26 2008
Categories: Homo sapiens | Single protein | U-plasminogen activator | Callaghan, O. | Chessari, G. | Congreve, M. | Cowan, S.R. | Frederickson, M. | Matthews, J.E. | Mcmenamin, R. | Smith, D. | Vinkovic, M. | Wallis, N.G. | ACT | D56 | Blood coagulation | Egf-like domain | Fibrinolysis | Glycoprotein | Hydrolase | Inhibitor | Kringle | Pharmaceutical | Phosphorylation | Plasminogen activation | Polymorphism | Protease | Secreted | Serine protease | Urokinase-type plasminogen activator | Zymogen
