Matrix metalloproteinase selectivity

GOTO T, MAEDA H and TANAKA T (2002) A Selective inhibitor of matrix metalloproteinases inhibits the migration of isolated osteoclasts by increasing the life span of podosomes. J Bone Miner Metab. 20 (2) 98-105. 

Matter, H. and Schwab, W. Affinity and selectivity of matrix metalloproteinase inhibitors a chemometrical study from the perspective of ligands and proteins. 

K. W. Peng, R. Vile, F. L. Cosset, and S. Russell, Selective transduction of protease-rich tumors by matrix-metalloproteinase-targeted retroviral vectors, Gene Ther. 6 1552 (1999). 

Li CW, Cantor WJ, Robinson R, etal. Matrix metalloproteinase inhibitor GM600I selectively reduces intimal hyperplasia and intima collagen in stented but not balloon treated arteries. Can J Cardiol 2000 16(suppl F) I43E... 

G. E. Terp, G. Cruciani, I. T. Christensen, F. S. Jorgensen, Structural differences of matrix metalloproteinases with potential implications for inhibitor selectivity examined by the GRID/... 

I. T, Jorgensen, E. S. Structural Differences of Matrix Metalloproteinases with Potential Implications for Inhibitor Selectivity Examined by the GRID/ CPCA Approach,/. Med. Chem. 2002,... 

Brown S, Meroueh SO, Fridman R, Mobashery S. Quest for selectivity in inhibition of matrix metalloproteinases. Curr. Topics... 

Yoshiyama Y, Asahina M, Hattori T (2000) Selective distribution of matrix metalloproteinase-3 (MMP-3) in Alzheimer s disease brain. Acta Neuropathol (Berl) 99 91-95. 

Pirard, B. (2007) Insight into the structural determinants for selective inhibition of matrix metalloproteinases. Drug Discovery Today, 12, 640-646. 

A series of phenoxyphenyl sulfone A-formylhydroxy-lamines was identified that contained potent and selective matrix metalloproteinase (MMP) inhibitors. Compound 27 displayed remarkable selectivity for both MMP-2 and MMP-9 over the undesired MMP-1. Unfortunately, 27 had no oral bioavailability. SAR modifications revealed that diol 28 maintained ideal selectivity, but suffered from low plasma exposure in monkey and a short in vivo half-life. Further modification showed that acetonide 29 had the desired selectivity for MMP-2 and MMP-9 and also displayed an optimal PK profile in monkeys with a plasma concentration 18-fold higher than 28. Oral bioavailabilities for 29 were >70% in rat, dog, and monkey. 

Wada, C. K., Holms, J. H., Curtin, M. L. et al. Phenoxyphenyl sulfone 7V-formylhydroxylamines (retrohydroxamates) as potent, selective, orally bioavailable matrix metalloproteinase inhibitors. J. Med. Chem. 2002, 45, 219-232. 

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