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The Discovery of MMP7 Inhibitors Exploiting a Novel Selectivity Trigger
Author(s) -
Edman Karl,
Furber Mark,
Hemsley Paul,
Johansson Cristian,
Pairaudeau Garry,
Petersen Jens,
Stocks Michael,
Tervo Anu,
Ward Alison,
Wells Edward,
Wissler Lisa
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000550
Subject(s) - selectivity , drug discovery , chemistry , computational biology , high throughput screening , potency , combinatorial chemistry , nanotechnology , biochemistry , biology , materials science , in vitro , catalysis
Trigger happy! High‐throughput screening was used to identify selective MMP7 inhibitors. Subsequent analysis by X‐ray crystallography revealed the underlying features for the selectivity trigger, unique to MMP7. In addition, further structural studies increased the understanding of the plasticity of the MMP7 active site. Finally, a single round of chemistry resulted in compounds with improved potency and retained selectivity.