Hot Natural Products & Bioactive Compounds

Selective inhibitor of MMP-2 that displays ~ 600-fold selectivity over MMP-1 (IC50 values are 0.81 and 486 nM respectively).

Broad spectrum MMP inhibitor (IC50 values are 0.7, 0.9, 13, 16 and 1170 nM for MMP-2, MMP-13, MMP-9, MMP-3 and MMP-1 respectively). Attenuates early left ventricular dilation after experimental myocardial infarction in mice.

Selective ADAM10 metalloprotease inhibitor; displays over 100-fold higher potency at ADAM10 compared to ADAM17. Blocks constitutive release of IL-6R, CX3CL1 and CXCL16 in cell-based cleavage experiments. Inhibits calcium ionophore-induced betacellulin shedding in IMPE cells. Prevents E-cadherin cleavage in A549 cells. Inhibits ADAM10 mediated neuronal outgrowth of dorsal root ganglion neurons in vitro.

Broad spectrum MMP inhibitor; K_i values are 0.45, 0.73, 1.1, 1.1, 2.1, 42 and 2500 nM for MMP-12, MMP-2, MMP-8, MMP-13, MMP-9, MMP-3 and MMP-7 respectively and IC₅₀ = 1600 nM for MMP-1). Displays no activity at other proteases up to a concentration of 100 <span class='symbol'>&mu;</span>M. Exhibits antiangiogenic and anti-invasive properties on lung metastasis of murine renal cell carcinoma.

Broad spectrum MMP inhibitor. Displays high affinity for MMP-2, -3 and -13 (IC50 values are 4, 7 and 8 nM respectively) and exhibits > 750-fold selectivity over MMP-1, -7 and -9. Attenuates left ventricular remodelling and dysfunction in rat model of heart failure.

Cipemastat is a potent, competitive inhibitor of human collagenases 1, 2 and 3 with Kis of 3.0, 4.4 and 3.4 nM, respectively.Cipemastat (Ro 32-3555) is a potent, competitive inhibitor of human matrix metalloproteinases. Cipemastat is selective for collagenase 1, 2 and 3 relative to related matrix metalloproteinases. Cipemastat is also a potent inhibitor of rat collagenase (IC₅₀=44.7±3.4 nM (n=4)). In vitro cartilage degradation ± inhibited IL-1a induced cartilage degradation in vitro in a concentration-dependent manner with an IC₅₀=60 nM. The inhibition is not mediated by a cytotoxic action on explant chondrocytes. Cipemastat, at all concentrations tested, fail 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±4.2 nM/mg and this decreases in cartilages implanted in vehicle-dosed animals to 53.6±7.1 nM/mg over a fourteen day period. Animals administered Cipemastat orally at doses of 2.5, 5, 10 and 25 mg/kg show statistically increased levels of implanted cartilage hydroxypro-line. Fourteen days after the second challenge injection of <i>P. acnes</i>, the area of cartilage most consistently affected by pannus is the lateral femoral condyle, which is the area analysed. In non-arthritic animals the mean cartilage area is 0.17±0.02 mm² (n=5). In arthritic animals there is a significant decrease to a mean area of 0.086±0.01 mm² (n=10). 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±0.019 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 secondary phase occurrs between day 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

Potent and selective inhibitor of MMP-3 (IC50 = 5.9 nM). Displays selectivity over a range of MMPs (IC50 values are 73, 840, 1790, 1900 and 51000 for MMP-13, MMP-9, MMP-2, MMP-14 and MMP-1 respectively).

Highly selective MMP-3 and MMP-12 inhibitor (IC₅₀ values are 0.023, 0.042, 1.75, 2.3, 5.8, 30.4, 34.2 and 66.9 <span class='symbol'>&#956;</span>M at MMP 3, 12, 8, 13, 7, 9, 2 and 14 respectively.) Inhibits fibronectin cleavage (IC₅₀ = 320 nM) and has little effect on keratinocyte migration <em>in vitro</em>. Substantially inhibits MMP-3 in an <em>ex vivo</em> model of chronic dermal ulcers.