The application of x-ray, NMR, and molecular modeling in the design of MMP inhibitors.
The following review discusses the successful application of X-ray, NMR, and molecular modeling in the design of potent and selective inhibitors of matrix metalloproteinases (MMPs) and TNFalpha-converting enzyme (TACE) from Wyeth. The importance of protein and ligand mobility as it impacts structure-based design is also discussed. The MMPs are an active target for a variety of diseases, including cancer and arthritis.
Structural Biology & Computational Chemistry, Department of Chemical & Screening Sciences, Wyeth Research, 87 Cambridge Park Dr. Cambridge, MA, 02140, USA. trush@wyeth.com
Thomas S
TS
Rush
Robert
R
Powers
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D014961:X-Ray Diffraction
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human