Z-Phe-Tyr-CHO | Cathepsin L inhibitor

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 (K_is=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

References/Citations

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 resorption 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