CP-471474

CP-471474 is an orally active and pan MMP inhibitor, with IC50 values of 1170 nM (MMP-1), 0.7 nM (MMP-2), 16 nM (MMP-3), 13 nM (MMP-9) and 0.9 nM (MMP-13), respectively[1][2].

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Metabolic Enzyme/Protease >> MMP

MMP-2:0.7 nM (IC50)

MMP-13:0.9 nM (IC50)

MMP-9:13 nM (IC50)

MMP-3:16 nM (IC50)

MMP-1:1170 nM (IC50)

CP-471474 plasma levels following subcutaneous injection are 2,020 ng/mL (1 h postdose) to 160 ng/mL (6 h postdose)[2]. CP-471,474 significantly reduces both the extent and severity of inflammation at 2 months. At 4 months, a spontaneous reduction of the inflammatory response is observed in both treated and untreated animals, and consequently no difference is observed between both[2]. CP-471474 significantly decreases the destructive lesions mainly at 2 months and also at 4 months[2]. Animal Model: Guinea pigs weighing 400 to 450 g (COPD)[2]. Dosage: 20 mg/kg (also supplemented daily by the diet (200 mg/200 g powdered chow)). Administration: Subcutaneously (in 20% ethanol/80% polyethylene glycol), once a day during the entire course. Result: Lungs derived from smoking animals treated with the compound demonstrated a statistically significant reduction in the destructive lesions. Showed an increase of both pro–MMP-9 and its active form (lanes 5 to 8) as compared with control animals.

[1]. L E Rohde, et al. Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice. Circulation. 1999 Jun 15;99(23):3063-70.

[2]. Moisés Selman, et al. Matrix metalloproteinases inhibition attenuates tobacco smoke-induced emphysema in Guinea pigs. Chest. 2003 May;123(5):1633-41.