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2viv
From Proteopedia
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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
2VIV 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 Feb 21 18:56:25 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 | VG2 | Blood coagulation | Egf-like domain | Fibrinolysis | Glycoprotein | Hydrolase | Inhibitor | Kringle | Pharmaceutical | Phosphorylation | Plasminogen activation | Polymorphism | Protease | Secreted | Serine protease | Urokinase-type plasminogen activator | Zymogen
