ONO-4817

ONO-4817 is an inhibitor of matrix metalloproteinase-2 (MMP-2) and MMP-9 (IC₅₀s = 0.5 and 0.8 nM, respectively, for the human enzymes).¹ It is selective for MMP-2 and -9 over MMP-3 and -1 (IC₅₀s = 26 and 2,500 nM, respectively). ONO-4817 (5 µg/ml) decreases bronchoalveolar lavage fluid (BALF) neutrophil infiltration in an ex vivo rat model of pulmonary ischemia-reperfusion injury.² It inhibits intra-artricular LPS-induced release of proteoglycans in knee joints in a guinea pig model of arthritis when administered at doses of 30 and 100 mg/kg.³ ONO-4817 (1% in the diet) reduces the number of lung metastases in a PC14PE6 lung cancer mouse xenograft model.⁴

WARNING This product is not for human or veterinary use.

1. Yamamoto, S., Nakatani, S., Ikura, M., et al. Design and synthesis of an orally active matrix metalloproteinase inhibitor. Bioorg. Med. Chem. 14(18), 6383-6403 (2006).

2. Shimoyama, T., Tabuchi, N., Chung, J., et al. Matrix metalloproteinase inhibitor (ONO-4817) attenuates ischemia-reperfusion injury in rat lung. Med. Sci. Monit. 12(2), BR51-BR56 (2006).

3. Yamada, A., Uegaki, A., and Ogawa, K. ONO-4817, an orally active matrix metalloproteinase inhibitor, prevents lipopolysaccharide-induced proteoglycan release from the joint cartilage in guinea pigs. Inflamm. Res. 49(4), 144-146 (2000).

4. Shiraga, M., Yano, S., Yamamoto, A., et al. Organ heterogeneity of host-derived matrix metalloproteinase expression and its involvement in multiple-organ metastasis by lung cancer cell lines. Cancer Res. 62(20), 5967-5973 (2002).