A potent and selective cathepsin L inhibitor
Cathepsin L inhibitor is a potent inhibitor of cathepsin L (IC50 = 0.85 nM). [1]? It is selective for cathepsin L over calpain II and cathepsin B (IC50s = 184, and 85.1 nM, respectively). It is trypanocidal with an ED50 value of 45 nM against T. brucei that is well below the ED50 value of 21,500 nM for human HL-60 cells. [2] Cathepsin L inhibitor completely suppresses osteoclastic pit formation on femur slices isolated from bovine cortical bone at a concentration of 1 μg/ml., [1][3] In vivo, cathepsin L inhibitor (2.5-10 mg/kg) inhibits bone loss in a mouse model of osteoporosis in a dose-dependent manner.
Reference:
[1]. Woo, J.-T., Sigeizumi, S., Yamaguchi, K., et al. Peptidyl aldehyde derivatives as potent and selective inhibitors of cathepsin L. Bioorganic Med. Chem. Lett. 5(14), 1501-1504 (1995).
[2]. Nkemngu, N.J., Grande, R., Hansell, E., et al. Improved trypanocidal activities of cathepsin L inhibitors. Int. J. Antimicrob. Agents 22(2), 155-159 (2003).
[3]. Woo, J.-T., Yamaguchi, K., Hayama, T., et al. Suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone resorption in vitro and in vivo. Eur. J. Pharmacol. 300(1-2), 131-135 (1996).
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