Cipemastat is a competitive inhibitor of human collagenases 1, 2, and 3 (Kis: 3.0, 4.4, and 3.4 nM).

Gelatinase B:59.1 nM (ki), Gelatinase A:154 nM (ki), Collagenases 1:3.0 nM (ki), MMP3:527 nM (ki), Collagenases 3:3.4 nM (ki), Collagenases 2:4.4 nM (ki)

Cipemastat (Ro 32-3555) is also a potent inhibitor of rat collagenase (IC50: 44.7 nM). In vitro cartilage degradation ± inhibited IL-1a induced cartilage degradation in vitro in a concentration-dependent manner (IC50: 60 nM). The inhibition is not mediated by a cytotoxic action on explant chondrocytes. Cipemastat, at all concentrations tested, fails to modify glucose utilization when compared to explants cultured in the presence of IL-La alone.

The amount of hydroxyproline in non-implanted cartilage is 119.3 nM/mg and this decreases in cartilages implanted in vehicle-dosed animals to 53.6 nM/mg over a fourteen-day period. Animals administered Cipemastat orally at doses of 2.5, 5, 10, and 25 mg/kg showed statistically increased levels of implanted cartilage hydroxyproline. Fourteen days after the second challenge injection of P. acnes, the area of cartilage most consistently affected by pannus is the lateral femoral condyle, which is the area analyzed. In arthritic animals, there is a significant decrease to a mean area of 0.086±0.01 mm2 (n=10). In non-arthritic animals, the mean cartilage area is 0.17±0.02 mm2 (n=5). The group of animals dosed with Cipemastat (50 mg/kg, p.o.) show a significantly greater area of cartilage with a mean value of 0.126±0.012 mm2 (n=9). The pannus area in vehicle-dosed animals is 0.099±0.017 mm2 and in Cipemastat dosed animals 0.102 mm2. Adjuvant arthritis injection of adjuvant-induced two phases of swelling of the injected paw in vehicle-dosed rats. The primary swelling phase occurred between days 0 to 5 and induced an increase in paw volume of 1.9±0.1 mL; the second phase occurs between days 9 to 14 and there was an increase in paw swelling of 0.98±0.08 mL. The group of animals dosed with dexamethasone (0.1 mg/kg) shows a significant reduction in both primary (0.2±0.03 mL) and secondary inflammation (0.07±0.08 mL) paw swelling as well as total inhibition of the lesion score.