| Bioactivity | L-006235 (L-235) is a potent, selective, reversible and orally active inhibitor of cathepsin K, with an IC50 of 5 nM in bone resorption assay. L-006235 shows selectivity for cathepsin K (Ki=0.2 nM) over cathepsin B, cathepsin L, and cathepsin S (Ki=1, 6, and 47 μM, respectively). L-006235 can reduce collagen degradation and prevent bone loss[1][2]. | ||||||||||||
| Invitro | L-006235 inhibits bone resorption in the rabbit bone resorption assay, with an IC50 of 5 nM[1].L-006235 (10 μM; 1 h) show a punctate fluorescence throughout the cytoplasm in HepG2 cells[2]. | ||||||||||||
| In Vivo | L-006235 (0.6-15 mg/kg; p.o. qd for 8-11 d) reduces N-telopeptides (NTx) and creatinine (Cre) by up to 76% dose-dependently in rhesus monkey[1].L-006235 (20 mg/kg; p.o.) exhibits high oral bioavailability (68%), long terminal half-life (204 min) and Cmax (1.4 μM) in rats[1]. Animal Model: | ||||||||||||
| Name | L-006235 | ||||||||||||
| CAS | 294623-49-7 | ||||||||||||
| Formula | C24H30N6O2S | ||||||||||||
| Molar Mass | 466.60 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Palmer JT, 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. [2]. Falgueyret JP, et, al. Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivity. J Med Chem. 2005 Dec 1;48(24):7535-43. [3]. Pennypacker BL, et, al. Cathepsin K inhibitors prevent bone loss in estrogen-deficient rabbits. J Bone Miner Res. 2011 Feb;26(2):252-62. |