L-006,235

L-006,235 is an orally bioavailable reversible inhibitor of cathepsin K (K_i(app) = 0.2 nM).¹ It is selective for cathepsin K over cathepsins B, -L, and -S (K_i(app)s = 1, 6, and 47 µM, respectively). In an in vitro bone resorption assay, L-006,235 inhibits degradation of bovine bone by isolated rabbit osteoclasts (IC₅₀ = 5 nM). L-006,235 (10 mg/kg for 27 days) reduces the loss of lumbar vertebral bone mineral density by 13.3% in ovariectomized rabbits compared to control animals.² It also increases weight bearing, indicating analgesia, in a rat model of osteoarthritis pain when administered at a dose of 100 mg/kg.³

WARNING This product is not for human or veterinary use.

1. Palmer, J.T., Bryant, C., Wang, D.-X., et al. Design and synthesis of tri-ring P₃ benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin K. J. Med. Chem. 48(24), 7520-7534 (2005).

2. Pennypacker, B.L., Duong, L.T., Cusick, T.E., et al. Cathepsin K inhibitors prevent bone loss in estrogen-deficient rabbits. J. Bone Miner. Res. 26(2), 252-262 (2011).

3. Nwosu, L.N., Growler, P.R.W., Burston, J.J., et al. Analgesic effects of the cathepsin K inhibitor L-006235 in the monosodium iodoacetate model of osteoarthritis pain. Pain Rep. 3(6), e685 (2018).