Cathepsin K Inhibitor I

Biochem/physiol Actions

Reversible: yes

Product does not compete with ATP.

Target K_i: 22 nM against cathepsin K

Primary Targetcathepsin K

Cell permeable: yes

General description

A cell-permeable, symmetrical bis(acylamino)ketone compound that acts as a potent, selective, reversible inhibitor of cathepsin K (K_i, = 22 nM). Also shown to inhibit cathepsin K in stably transfected CHO cells (IC₅₀ = 134 nM). Reported to bind to cathepsin K and span both the S- and S′- subsites. Inhibits papain (K_i >10 µM), trypsin (K_i >50 µM), and chymotrypsin (K_i >50 µM) only at higher concentrations. Exhibits greater selectivity for cysteine proteases of the papain family (K_i = 340 nM, 890 nM, and 1-3 µM for cathepsin L, cathepsin S, and cathepsin B, respectively).

A cell-permeable, symmetrical bis(acylamino)ketone that acts as a potent, selective, and reversible inhibitor of cathepsin K (K_i,app = 22 nM). Shown to bind to cathepsin K and span both the S- and S′-subsites. A poor inhibitor of papain (K_i,app >10 µM) but displays greater selectivity towards other proteases of the papain family (K_i,app = 340 nM, 890 nM, and 1.3 µM for cathepsin L, cathepsin S, and cathepsin B respectively). Inhibits trypsin and chymotrypsin activities only at higher concentrations (K_i,app ≥ 50 µM).

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Claveau, D., et al. 2000. Biochem. Pharmacol.60, 759.LaLonde, J.M., et al. 1999. Biochemistry38, 862.Yamashita, D.S., et al. 1997. J. Am. Chem. Soc.119, 11351.

Packaging

Packaged under inert gas

5 mg in Plastic ampoule

Reconstitution

Following reconstitution aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Sequence

Cbz-Leu-NH-CH₂-CO-CH₂-NH-Leu-Cbz

Warning

Toxicity: Standard Handling (A)