2viw

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spinqualitylabelsall models PDB ID 2viw Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.05Å
Sites:	and
Ligands:	and
Activity:	U-plasminogen activator, with EC number 3.4.21.73
Coordinates:	save as pdb, mmCIF, xml

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. 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

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