Odanacatib

• 产品号: S1115
• CAS号: 603139-19-1
• 分子式: C25H27F4N3O3S
• 分子量: 525.5587928
• 保 存: -20°C

产品别名

• 标题: Odanacatib
• 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
• 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
• 别名: MK0822

产品登记号

• CAS号: 603139-19-1

产品性质

• 作用靶点: Cathepsin K
• 成盐信息: Free Base
• 保存条件: -20°C

产品详细信息

详细说明 (English)

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; Rabbit Cathepsin K
• IC50: 0.2 nM; 1 nM ^[1]
• 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 (V_dss: 1.1 L kg^-1), half-life (T_1/2: 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

• Protocol: 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.

References

• References: [1] Gauthier JY, et al. Bioorg Med Chem Lett. 2008, 18(3), 923-928.
• References: [2] Leung P, et al. Bone. 2011, 49(4), 623-635.
• References: [3] Pennypacker BL, et al. J Bone Miner Res. 2011, 26(2):252-262.
• References: [4] Masarachia PJ, et al. J Bone Miner Res. 2012, 27(3), 509-523.

参考文献

• Gauthier JY, et al. Bioorg Med Chem Lett. 2008, 18(3), 923-928.
• Leung P, et al. Bone. 2011, 49(4), 623-635.
• 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.