JNJ-63533054 是一种有效的,选择性的,具有口服活性的GPR139激动剂,对人GPR139的EC50为 16 nM。JNJ-63533054 对 GPR139 的选择性高于其他 GPCR,离子通道和转运蛋白。JNJ-63533054 可以穿过血脑屏障 (BBB)。
生物活性 | JNJ-63533054 is a potent, selective and orally activeGPR139agonist with anEC50of 16 nM forhumanGPR139(hGPR139). JNJ-63533054 shows selective forGPR139over other GPCRs, ion channels, and transporters. JNJ-63533054 can cross the blood-brain barrier (BBB)[1][2]. |
IC50& Target | EC50: 16 nM (Human GPR139), 63 nM (Rat GPR139) and 28 nM (Mouse GPR139)[1] |
体外研究 (In Vitro) | JNJ-63533054 specifically activates human GPR139 in the calcium mobilization (EC50of 16 nM) and GTPγS binding (EC50of 17 nM) assays. JNJ-63533054 also activates the rat and mouse GPR139 receptor with similar potency (rat EC50of 63 nM, mouse EC50of 28 nM)[1]. In a saturation study for human GPR139, a single population of high-affinity binding sites for [3H] JNJ-63533054 is observed (Kdof 10 nM). The Bmaxvalue is 26 pmol/mg of protein. Saturation studies for the rat GPR139 and mouse GPR139 yielded Kdvalues within the same range (32 nM and 23 nM, respectively; Bmax= 8.5 pmol/mg of protein and 6.2 pmol/mg of protein, respectively)[1].
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体内研究 (In Vivo) | JNJ-63533054 (3-30 mg/kg; oral administration; once; SD rats) treatment induces a dose-dependent reduction in locomotor activity in the first hour[1]. The pharmacokinetics of JNJ-63533054 (Compound 7c; 1 mg/kg iv; 5 mg/kg po) in rat is examined. The IV clearance is 53 mL/min/kg, the Cmaxis 317 ng/mL (~1 μM), the t1/2is 2.5 hours, and JNJ-63533054 is able to cross the blood-brain barrier (BBB) with a brain to plasma ratio (b/p) of 1.2[2].
Animal Model: | Male Sprague-Dawley rats (350-450 g)[1] | Dosage: | 3 mg/kg, 10 mg/kg, and 30 mg/kg | Administration: | Oral administration; once | Result: | Induced a dose-dependent reduction in locomotor activity in the first hour. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : ≥ 50 mg/mL(157.84 mM) *"≥" means soluble, but saturation unknown. 配制储备液 1 mM | 3.1568 mL | 15.7838 mL | 31.5676 mL | 5 mM | 0.6314 mL | 3.1568 mL | 6.3135 mL | 10 mM | 0.3157 mL | 1.5784 mL | 3.1568 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (7.89 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (7.89 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (7.89 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (7.89 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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