SB-649868

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Chemical Structure| 380899-24-1 同义名 : GSK649868
CAS号 : 380899-24-1
货号 : A600972
分子式 : C26H24FN3O3S
纯度 : 99%+
分子量 : 477.55
MDL号 : MFCD18251524
存储条件：

Pure form Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(219.87 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The orexin-1 (OX1) and orexin-2 (OX2) receptors are G-protein coupled receptors profoundly implicated in sleep disorders. SB-649868 is a dual OX1 and OX2 receptor antagonist with pKi values of 9.4 and 9.5 for human OX1 and OX2 receptors, respectively. It demonstrates higher functional potencies for rat OX1 and OX2 receptors with pKi values of 9.93 and 10.11, respectively. The in vitro clearance of SB-649868 in rat and human liver microsomes was 8.7 and 15.1mL/min/g, respectively. SB-649868 displaced [3H]almorexant in Chinese hamster ovary cells overexpressing both human recombinant OX1 and OX2 receptors in a concentration dependent manner, with pKi values of 9.12 and 8.89, respectively, In rats subjected to intracerebroventricular injection of neuropeptides orexin-A (OX-A), oral administration of SB-649868 (3 and 10mg/kg) 3 hours before OX-A injection resulted in a significant, dose-dependent reduction of OX-A induced grooming. In the circadian time model of male CD rats, SB-649868 treatment caused a dose-dependent reduction in sleep latency, with the maximal effect observed at 30mg/kg. SB-649868 at 10 and 30mg/kg also significantly increased total sleep time over the 5-hour testing period in a dose-dependent manner[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.09mL

0.42mL

0.21mL

10.47mL

2.09mL

1.05mL

20.94mL

4.19mL

2.09mL
参考文献

[1]Faedo S, Perdona E, et al. Functional and binding kinetic studies make a distinction between OX1 and OX2 orexin receptor antagonists. Eur J Pharmacol. 2012 Oct 5;692(1-3):1-9.

[2]Di Fabio R, Pellacani A, et al. Discovery process and pharmacological characterization of a novel dual orexin 1 and orexin 2 receptor antagonist useful for treatment of sleep disorders. Bioorg Med Chem Lett. 2011 Sep 15;21(18):5562-7.

[3]Di Fabio R, Pellacani A, Faedo S, Roth A, Piccoli L, Gerrard P, Porter RA, Johnson CN, Thewlis K, Donati D, Stasi L, Spada S, Stemp G, Nash D, Branch C, Kindon L, Massagrande M, Poffe A, Braggio S, Chiarparin E, Marchioro C, Ratti E, Corsi M. Discovery process and pharmacological characterization of a novel dual orexin 1 and orexin 2 receptor antagonist useful for treatment of sleep disorders. Bioorg Med Chem Lett. 2011 Sep 15;21(18):5562-7.