JNJ-55308942 是一种高亲和力、选择性、可透过血脑屏障的P2X7功能拮抗剂 (hP2X7:IC50=10 nM,Ki=7.1 nM; rP2X7:IC50=15 nM,Ki=2.9 nM)。JNJ-55308942 口服生物利用度高,可与大脑 P2X7 结合并阻断 IL-1β 从成年啮齿动物脑中释放。
生物活性 | JNJ-55308942 is a high-affinity, selective, brain-penetrantP2X7functional antagonist (hP2X7:IC50=10 nM,Ki=7.1 nM; rP2X7:IC50=15 nM,Ki=2.9 nM). JNJ-55308942 is orally bioavailable, binds to brain P2X7 and blocks IL-1β release from adult rodent brain[1][2]. |
体外研究 (In Vitro) | JNJ-55308942 shows pKis of 8.1and 8.5 for recombinant human and rat P2X7 channels, respectively. In human blood and in mouse blood and microglia, JNJ-55308942 attenuates IL-1β release in a potent and concentration-dependent manner[2].
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体内研究 (In Vivo) | JNJ-55308942 (30 mg/kg; p.o.) attenuates LPS-induced microglial activation in mice[2]. In a model ofBacillus Calmette-Guerin(BCG)-induced depression, JNJ-55308942 dosed orally (30 mg/kg), reversed the BCG-induced deficits of sucrose preference and social interaction. After oral dosing, the compound exhibited both dose and concentration-dependent occupancy of rat brain P2X7 with an ED50of 0.07 mg/kg. The P2X7 antagonist (3 mg/kg, oral) blocked Bz-ATP-induced brain IL-1β release in conscious rats, demonstrating functional effects of target engagement in the brain[2]. JNJ-55308942 (5 mg/kg; p.o.) shows the F, Vss, CL, Cmaxand AUC24hvalues are 81%, 1.7 L/kg, 3.7 mL min/kg, 1747 ng/mL, and 17549 (ng/mL) h, respectively[1].
Animal Model: | Sixteen male C57/BL6J mice[2] | Dosage: | 30 mg/kg | Administration: | P.o. (after an i.p. injection of LPS (0.8 mg/kg, i.p.)) | Result: | Significantly attenuated the effect of LPS on FSC, CD45 surface expression and CD11b surface expression. |
Animal Model: | Rat[1] | Dosage: | P.o. (Pharmacokinetic Analysis) | Administration: | 5 mg/kg | Result: | The F, Vss, CL, Cmaxand AUC24hwere 81%, 1.7 L/kg, 3.7 mL min/kg, 1747 ng/mL, and 17549 (ng/mL) h, respectively. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | 4°C, sealed storage, away from moisture and light *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light) |
溶解性数据 | In Vitro: DMSO : 100 mg/mL(235.12 mM;Need ultrasonic) 配制储备液 1 mM | 2.3512 mL | 11.7559 mL | 23.5117 mL | 5 mM | 0.4702 mL | 2.3512 mL | 4.7023 mL | 10 mM | 0.2351 mL | 1.1756 mL | 2.3512 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 (sealed storage, away from moisture and light)。-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: ≥ 4 mg/mL (9.40 mM); Clear solution
此方案可获得 ≥ 4 mg/mL (9.40 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 40.0 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% (20%SBE-β-CDin saline) Solubility: ≥ 4 mg/mL (9.40 mM); Clear solution
此方案可获得 ≥ 4 mg/mL (9.40 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 40.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 4 mg/mL (9.40 mM); Clear solution
此方案可获得 ≥ 4 mg/mL (9.40 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 40.0 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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