Description
CP 471,474 is a broad-spectrum inhibitor of matrix metalloproteinases (MMPs) with IC50 values of 0.7, 16, 13, and 0.9 nM for MMP-2, MMP-3, MMP-9, and MMP-13, respectively. It is selective for these MMPs over MMP-1 (IC50 = 1,170 nM). CP 471,474 reduces left ventricular enlargement and decreases the incidence of cardiac rupture in mouse models of myocardial infarction when administered at doses of 120 mg/kg twice per day and 240 mg/kg per day, respectively.
Biochem/physiol Actions
CP-471474 is a broad spectrum inhibitor of matrix metalloproteinases. CP-471474 has a low nM IC50 efficacy for MMP-2, MMP-3, MMP-9, and MMP-13. CP-471474 has low potency against MMP-1 (IC50 > 1 uM). CP-471474 prevents left ventricular remodeling after experimental myocardial infarction in mice. CP-471474 also inhibits cigarette smoke-induced lung inflammation and the progression of emphysema in guinea pig models.
References
[1] L E ROHDE. Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice.[J]. Circulation, 1999, 99 23: 3063-3070. DOI:
10.1161/01.cir.99.23.3063[2] LU FANG . Differences in inflammation, MMP activation and collagen damage account for gender difference in murine cardiac rupture following myocardial infarction[J]. Journal of molecular and cellular cardiology, 2007, 43 5: Pages 535-544. DOI:
10.1016/j.yjmcc.2007.06.011
