ONO-5334

ONO-5334 is a potent, selective and orally active cathepsin K inhibitor with K_i values of 0.10 nM, 0.049 nM and 0.85 nM for human, rabbit and rat cathepsin K, respectively. ONO 5334 is an effective antiviral compound against SAR-COV-2 virus activity with an EC₅₀ value of 500 nM. ONO-5334 has the potential for the study of osteoporosis and COVID-19 disease^[1]. IC50 & Target:Ki: 0.10 nM (human cathepsin K)
Ki: 0.049 nM (rabbit cathepsin K)
Ki: 0.85 nM (rat cathepsin K)^[1] In Vitro: ONO-5334 has inhibitory effects on human cathepsin S, human cathepsin L, human cathepsin B, porcine calpain Ι and porcine calpain II with K_i values of 0.83 nM, 1.7 nM, 32 nM, 82 nM and 69 nM, respectively^[1].
ONO-5334 (0.1-1 μM; 24 hours) suppresses human osteoclast-mediated bone resorption. It potently reduces osteoclast-mediated release of CTX from bone slices as a dose dependent manner^[1].
ONO-5334 (0-10 μM; pre-treated for 16 h) inhibits antiviral activities in a discernable dose-dependent manner in Vero E6 cells by designed to capture multicycle replication, exhibiting an EC₅₀ value of 0.5 μM^[2]/
In Vivo: ONO-5334 (oral administration; 0.12-15 mg/kg; single dose) can dose-dependently reduce PTHrP-induced increase in plasma calcium with significant effect (86% reduction) at 15 mg/kg. It also reduces PTHrP-induced increase in plasma CTX level in TPTX rats by 90% at 15 mg/kg^[1].
ONO-5334 (oral administration; 0.3-30 mg/kg; 7 consecutive days) at 3 mg/kg or 30 mg/kg significantly decreases CTX (a bone resorption marker) concentration. On day 7, the reduction in serum CTX concentration by ONO-5334 at 3 mg/kg and 30 mg/kg was 62% and 79%, respectively^[1].