The identification of beta-hydroxy carboxylic acids as selective MMP-12 inhibitors.
A new class of selective MMP-12 inhibitors have been identified via high throughput screening. Crystallization with MMP-12 confirmed the mode of binding and allowed initial optimization to be carried out using classical structure based design.
Holmes
Ian P
IP
GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom.
Gaines
Simon
S
Watson
Steve P
SP
Lorthioir
Olivier
O
Walker
Adam
A
Baddeley
Suzanne J
SJ
Herbert
Shane
S
Egan
Danielle
D
Convery
Máire A
MA
Singh
Onkar M P
OM
Gross
Jeffrey W
JW
Strelow
John M
JM
Smith
Robert H
RH
Amour
Augustin J
AJ
Brown
David
D
Martin
Stephen L
SL
D000818:Animals; D001665:Binding Sites; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D015195:Drug Design; D006168:Guinea Pigs; D006801:Humans; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D053508:Matrix Metalloproteinase 12