Quest for selectivity in inhibition of matrix metalloproteinases.
Matrix metalloproteinases (MMPs), of which at least 26 are known in humans, have been linked to a number of pathological conditions including tumor metastasis, inflammation, neurological and cardiovascular diseases. Inhibition of MMPs has been widely sought as a strategy in intervention of these disease processes. Whereas a large number of broad-spectrum MMP inhibitors have been developed over the past decade, these inhibitors have not met the promise and expectations in clinical trials. The broad-spectrum inhibition, which besides MMPs often targets other metalloproteinases, has been considered one of the potential problems that affects the therapeutic efficacy of MMPs inhibitors. Several MMP inhibitors that show selectivity for various MMPs have been reported in the past few years. This report describes the structural and inhibitory properties of these novel inhibitors, which hold considerable promise for effective targeting of these important enzymes.
Department of Chemistry and Biochemistry, 423 Nieuwland Science Center, University of Notre Dame, IN 46556, USA.
Stephen
S
Brown
Samy O
SO
Meroueh
Rafael
R
Fridman
Shahriar
S
Mobashery
D000818:Animals; D015195:Drug Design; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013379:Substrate Specificity
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases