物质信息

ID:74046

名称和标识
IUPAC标准名
(2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-{[(1S)-2,2,2-trifluoro-1-[4-(4-methanesulfonylphenyl)phenyl]ethyl]amino}pentanamide
别名
Odanacatib MK0822
IUPAC传统名
(2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-{[(1S)-2,2,2-trifluoro-1-[4-(4-methanesulfonylphenyl)phenyl]ethyl]amino}pentanamide
数据登录号
化合物性质
安全信息
保存条件
-20°C
产品相关信息
成盐信息
Free Base
药理学性质
作用靶点
Cathepsin K
描述信息
Research Area
Description
Neurological Disease
Biological Activity
Description
Odanacatib (MK 0822) is a potent, selective, and neutral inhibitor of human and rabbit cathepsin K with IC50 of 0.2 nM and 1 nM , respectively.
Targets
Human Cathepsin K
IC50
0.2 nM
In Vitro
In vitro, Odanacatib shows the high inhibitory activity and selectivity on cathepsin K with IC50 values of 0.2 nM and 1 nM for human cathepsin K and rabbit cathepsin K, respectively. Furthermore, Odanacatib also shows similar potencies in whole human cell enzyme occupancy assays with corrected IC50 of 5 nM. [1] A recent study shows that Odanacatib results in reduction of Osteoclast (OC) resorption activity by interrupting intracellular vesicular trafficking. [2]
In Vivo
In preclinical rats, Odanacatib (10 mg/kg) exhibits excellent pharmacokinetics with clearance (Cl: 2 mL kg-1 min-1), low volume of distribution (Vdss: 1.1 L kg-1), half-life (T1/2: 6 hours) and oral bioavailability (F: 8%), respectively. Besides, Odanacatib also exhibits excellent metabolic stability in rat hepatocytes with a 96% recovery of the parent identity. [1] Odanacatib (ODN) administrated by p.o. prevents bone loss in ovariectomized (OVX) rabbits in a dose-related manner. Moreover, Odanacatib (9?μM/day) leads to a significant increase in proximal femur bone mineral density (BMD) (7.8%), femoral neck BMD (10.8%) and the greater trochanter BMD (6.5%). [3] In the estrogen-deficient, skeletally mature rhesus monkeys, long-term treatment with Odanacatib effectively inhibits bone turnover without reducing osteoclast number and maintains normal biomechanical properties of the spine of OVX nonhuman primates. [4]
Clinical Trials
Odanacatib (MK 0822) is currently in Phase I clinical trials in patients with Osteoporosis. Combination of Odanacatib (MK 0822), cholecalciferol andcalcium carbonate is currently in Phase II clinical trials in patients with Osteoporosis Postmenopausal.
Features
Odanacatib (MK 0822) is a potent, selective, and neutral cathepsin K inhibitor.
Protocol
Kinase Assay []
Cell Assay []
Animal Study [3]
Animal Models
Ovariectomized (OVX) rabbit model
Formulation
Odanacatib is provided in a diet formulae.
Doses
≤9?μM/day
Administration
Administered via p.o.
分子图谱
暂无数据
点击上传数据
参考文献
• Pennypacker BL, et al. J Bone Miner Res. 2011, 26(2):252-262.
• Masarachia PJ, et al. J Bone Miner Res. 2012, 27(3), 509-523.
• Gauthier JY, et al. Bioorg Med Chem Lett. 2008, 18(3), 923-928.
• Leung P, et al. Bone. 2011, 49(4), 623-635.
导 航