ONO-5334 is a selective, orally active and potent histone K inhibitor with anti-SAR-COV-2 and anti-bone resorption activity for the study of osteoporosis.

Cathepsin K (rabbit):0.049 nM (Ki), Cathepsin K (rat):0.85 nM (Ki), Cathepsin K (human):0.10 nM (Ki)

ONO-5334 inhibits human cathepsin S, L, and B, and porcine calpain Ι and II (Ki: 0.83 nM, 1.7 nM, 32 nM, 82 nM, and 69 nM, respectively). ONO-5334 (0.1-1 μM; 24 hours) also inhibits human osteoclast-mediated bone resorption, effectively decreasing the osteoclast-mediated release of CTX from bone slices in a dose-dependent manner[1].

ONO-5334 (oral; 0.3-30 mg/kg; 7 consecutive days) at doses of 3 mg/kg or 30 mg/kg significantly reduced CTX (bone resorption marker) concentrations.ONO-5334 (oral; 0.12-15 mg/kg; single dose) dose-dependently reduced PTHrP-induced elevation of plasma calcium, with a significant effect at 15 mg/kg (86% reduction). It also reduced the PTHrP-induced increase in plasma CTX levels in TPTX rats by 90% at 15 mg/kg. On day 7, ONO-5334 (3 mg/kg and 30 mg/kg) reduced serum CTX concentrations by 62% and 79%, respectively[1].