2vip

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spinqualitylabelsall models PDB ID 2vip Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 1.72Å
Sites:	, and
Ligands:	, ,
Activity:	U-plasminogen activator, with EC number 3.4.21.73
Related:	2VIV, 1C5X, 1GJ9, 2VIO, 1W0Z, 1FV9, 1VJA, 1GJ8, 1W11, 1SQO, 1GJD, 1W10, 1OWK, 1W12, 1GI9, 1O5A, 1C5Z, 1OWJ, 1GI7, 1O5B, 1GJC, 1SC8, 1GJA, 1O3P, 1OWE, 1SQA, 1GJB, 2VIW, 1F92, 1OWI, 1KDU, 2VIN, 1SQT, 1F5L, 1OWD, 1EJN, 2VIQ, 1LMW, 1U6Q, 1GI8, 2JDE, 1C5Y, 1W14, 1VJ9, 1W13, 1GJ7, 1C5W, 1OWH, 1O5C
Resources:	FirstGlance, OCA, PDBsum, RCSB
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

2VIP 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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