ONO-5334

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效、选择性、口服活性的组织蛋白酶 K 抑制剂，对人、兔和大鼠组织蛋白酶 K 的 Ki 值分别为 0.1 nM、0.049 nM 和 0.85 nM。

A potent, selective, orally active inhibitor of cathepsin K with Ki of 0.1 nM, 0.049 nM and 0.85 nM for human, rabbit and rat cathepsin K, respectively; shows less or no potentcy for human cathepsin S/L/B/C (Ki=0.83/1.7/32/2500 nM); inhibits human osteoclasts bone resorption in vitro at a concentration more than 100 fold lower than that of alendronate; reduces plasma calcium level increased by PTHrP in thyroparathyroidectomized rats, decreases serum and urine C-telopeptide of type I collagen level.Osteoporosis Phase 2 Discontinued.

ONO-5334 has inhibitory effects on human cathepsin S, human cathepsin L, human cathepsin B, porcine calpain Ι and porcine calpain II with Ki values of 0.83 nM, 1.7 nM, 32 nM, 82 nM and 69 nM, respectively.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.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.Cell Viability Assay Cell Line:Vero E6 cells Concentration:0.001 μM, 0.003 μM, 0.1 μM, 0.3 μM, 1 μM, 2.5 μM Incubation Time:Pre-treated for 16 h and then cultured for 24 hours Result:Inhibited SARS-COV-2 virus replication in a dose-dependent manner.

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.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. Animal Model:Monkey Dosage:0.3 mg/kg; 3 mg/kg Administration:Oral administration; 7 consecutive days Result:Reduced bone resorption markers but not bone formation markers in normal monkeys.

ONO5334 | ONO 5334

Metabolic Enzyme/Protease

Cathepsin

Cathepsin

Metabolic Disease

Osteoporosis

868273-90-9

438.59

C21H34N4O4S

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (114.00 mM)

O=C(N/N=C1SC[C@@H](C)N\1C)C([C@@H](NC(C2CCCCCC2)=O)C3CCOCC3)=O

N-((S)-1-cyclohexyl-3-(2-((R,Z)-3,4-dimethylthiazolidin-2-ylidene)hydrazinyl)-2,3-dioxopropyl)cycloheptanecarboxamide

(-20℃)

With Ice Pack

≥ 2 years