Z-Phe-Tyr-CHO (167498-29-5) is a potent and selective inhibitor of cathepsin L, IC50=0.85 nM 1 selective over ?cathepsin B and calpain II (IC50s=85.1 and 184 nM respectively). Suppresses osteoclastic ?pit formation at 1.5 nM and markedly inhibited parathyroid hormone-stimulated osteoclastic bone resorption.2 Also inhibits cathepsin K (Kis=0.052 and 1.57 nM for cat L and cat K respectively) and partially provides the basis for the finding that cathepsin K is the protease responsible for osteoclastic bone resorption.3 Provides partial protection against serum and potassium deprivation-induced neuronal death.4 Active in vivo.2
1) Woo et al. (1995), Peptidyl aldehyde derivatives as potent and selective inhibitors of cathepsin L; Bioorg. Med. Chem. Lett., 5 1501
2) Woo et al. (1996), Suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone resorption in vitro and in vivo; Eur. J. Pharmacol., 300 131
3) James et al. (2001) Potent and selective cathepsin L inhibitors do not inhibit human osteoclast resoption in vitro; J. Biol. Chem., 276 11507
4) Kaasik et al. (2005), Up regulation if lysosomal cathepsin L and autophagy during neuronal death induced by reduced serum and potassium; Eur. J. Neurosci., 22 1023
