Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13).
Computer aided drug design led to a new class of spiro-barbiturates (e.g., 4a, MMP-13 K(i)=4.7 nM) that are potent inhibitors of MMP-13.
Kim
Soong-Hoon
SH
Bristol Myers Squibb Co., Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08560, USA. soonghoon.kim@bms.com
Pudzianowski
Andrew T
AT
Leavitt
Kenneth J
KJ
Barbosa
Joseph
J
McDonnell
Patricia A
PA
Metzler
William J
WJ
Rankin
Bruce M
BM
Liu
Richard
R
Vaccaro
Wayne
W
Pitts
William
W
D001463:Barbiturates / Q000138:chemical synthesis* / Q000494:pharmacology; D003198:Computer Simulation; D017076:Computer-Aided Design; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D053509:Matrix Metalloproteinase 13; D061965:Matrix Metalloproteinase Inhibitors; D008958:Models, Molecular; D010003:Osteoarthritis / Q000188:drug therapy; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001463:Barbiturates; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D013141:Spiro Compounds; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13