N-[1-[[(Cyanomethyl)amino]carbonyl]cyclohexyl]-4-[2-(4-methyl-1-piperazinyl)-4-thiazolyl]benzamide

Uses

L 006235 is a cathepsin K inhibitor, which displays greater than 4000-fold selectivity against the lysosomal/endosomal antitargets cathepsin B, L, and S.

Biological Activity

l-006235 is a potent and selective inhibitor of cathepsin k.

in vitro

after dilution of l-006235 to 0.05 nm, the cathepsin k enzyme activity was initially inhibited, but slowly recovered with a first-order rate constant of 0.023 s-1. the final steady-state enzyme activity was 80-90% that of control, suggesting the complete reversibility of the l-006235-cathepsin k complex. l-006235 was found to be not a substrate for the nitrilase activity of cat k [1].

in vivo

l-006235 was orally bioavailable in rats, with a terminal half-life of over 3 h. l-006235 was orally dosed in ovariectomized rhesus monkeys once per day for 7 days. results showed that collagen breakdown products were dose-dependently reduced by up to 76%. plasma concentrations of l-006235 above the bone resorption ic50 after 24 h indicated a correlation between functional cellular and in vivo assays. these findings suggested that the inhibition of collagen breakdown by cathepsin k inhibitors, such as l-006235, might be useful in osteoporosis and other indications involving bone resorption [1].

IC 50

0.25 nm

storage

Store at +4°C

References

[1] palmer jt,bryant c,wang dx et al. design and synthesis of tri-ring p3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin k. j med chem.2005 dec 1;48(24):7520-34.