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JD-5037

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Chemical Structure| 1392116-14-1 同义名 : -
CAS号 : 1392116-14-1
货号 : A862077
分子式 : C27H27Cl2N5O3S
纯度 : 98%
分子量 : 572.506
MDL号 : MFCD30533451
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 250 mg/mL(436.68 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 cannabinoid 1 receptor (CB1R) is one of the most abundant G protein-coupled receptors (GPCRs) in the central nervous system, with key roles during neurotransmitter release and synaptic plasticity[3]. JD5037 is a novel peripherally restricted CB1 receptor (CB1R) inverse agonist being developed for the treatment of visceral obesity and its metabolic complication, including nonalcoholic fatty liver disease and dyslipidemia. JD5037 was administered by oral gavage at 10, 40, and 150 mg/kg/day dose levels for up to 34 days to Sprague Dawley rats, and higher incidences of stereotypic behaviors were observed in 10 mg/kg females and 40 mg/kg males, and slower responses for reflex and sensory tests were observed only in males at 10 and 40 mg/kg during neurobehavioral testing. Results showed highest dose resulted in lower AUCs indicative of non-linear kinetics[4]. JD5037 treatment of alcohol-drinking mice inhibits the formation of biologically active octanoyl-ghrelin without affecting its inactive precursor desacyl-ghrelin. In ghrelin-producing stomach cells, JD5037 reduced the level of the substrate octanoyl-carnitine generated from palmitoyl-carnitine by increasing fatty acid β-oxidation[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.75mL

0.35mL

0.17mL

8.73mL

1.75mL

0.87mL

17.47mL

3.49mL

1.75mL
参考文献

[1]Mukhopadhyay B, Schuebel K, et al. Cannabinoid receptor 1 promotes hepatocellular carcinoma initiation and progression through multiple mechanisms. Hepatology. 2015 May;61(5):1615-26.

[2]Chorvat RJ, Berbaum J, et al. JD-5006 and JD-5037: peripherally restricted (PR) cannabinoid-1 receptor blockers related to SLV-319 (Ibipinabant) as metabolic disorder therapeutics devoid of CNS liabilities. Bioorg Med Chem Lett. 2012 Oct 1;22(19):6173-80.

[3]Carlos Nogueras-Ortiz,et al. The Multiple Waves of Cannabinoid 1 Receptor Signaling. Mol Pharmacol. 2016. 90(5), 620-626.

[4]Kale, V. P., Gibbs, S. et al. Preclinical toxicity evaluation of JD5037, a peripherally restricted CB1 receptor invere agonist, in rats and dogs for treatment of nonalcoholic steatohepatitis. Regul Toxicol Pharmacol. 2019. 109, 104483.

[5]Grzegorz Godlewski,et al. Targeting Peripheral CB 1 Receptors Reduces Ethanol Intake via a Gut-Brain Axis. Cell Metab. 2019. 29(6), 1320-1333.