JNJ-78911118

JNJ-78911118（10 pM-10 μM，2 小时）以浓度依赖的方式取代海马神经元膜上与放射性配体 JNJ-74950343 结合的 GluN1/2A 界面，不改变谷氨酸的效力，但降低其对同源 GluN1/2A 受体的活性 [1]。JNJ-78911118（10 μM，24-72 小时）促进大鼠海马神经元培养物中神经突的生长和突触的形成，并在 72 小时后显著增强树突复杂性的多个指标 [1]。在包含 77 种离子通道、受体和转运蛋白的定制筛选板以及包含 373 种激酶的筛选板中，JNJ-78911118（1-10 μM）对所有靶点的抑制率均低于 50% [1]。

JNJ-78911118 (60 mg/kg，皮下注射，单次药物)可减弱弗氏完全佐剂 (CFA) 感应性疼痛模型中的机械性痛觉过敏，可抑制海马长时程增强作用，并增加前额叶皮层电流的微型兴奋性突触后频率 (mEPSC) [1]。 JNJ-78911118 (50 和 250 mg/kg，阈值，每日两次，连续4天或相同天两次)在队列中总体耐受性良好，但会产生模型相关的血流动力学效应[1]。

Animal/Disease Models: Male C57BL/6 N mice (8-12 weeks)[1]
Doses: 60 mg/kg
Route of Administration: s.c., single dose 2 days post-CFA
Experimental Results: Partly reversed CFA induced allodynia at 60 mg/kg, while Gabapentin (150 mg/kg, p.o.) completely reversed it. Reduced tactile allodynia at 30 min and 1 h post-administration compared to controls. Had no effect on paw withdrawal thresholds (PWTs) 24 h post-dosing.

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Animal/Disease Models: Wild-type C57BL/6J and homozygous Grin2a KO mice[1]
Doses: 60 mg/kg
Route of Administration: s.c., single dose 2 days post-CFA
Experimental Results: Mitigated CFA-induced allodynia in wild type mice at 30 min and 1-h post-administration. Did not significantly reduce CFA-induced mechanical allodynia in Grin2a KO mice.

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Animal/Disease Models: Male Sprague-Dawley rats (8-10 weeks)[1]
Doses: 60 mg/kg
Route of Administration: s.c., single dose 30 min pre-TBS
Experimental Results: Did not alter baseline synaptic transmission but completely blocked the induction of LTP by theta burst stimulation (TBS). The population spike amplitude remained at pre-stimulation levels throughout the recording period (50-60 min post-TBS).

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Animal/Disease Models: Male Sprague-Dawley rats (6-10 weeks)[1]
Doses: 60 mg/kg
Route of Administration: s.c., single dose (24 h before recording)
Experimental Results: Induced a significant decrease in the inter-event interval of mEPSCs in layer 5 pyramidal neurons in rat medial prefrontal cortex. Showed no significant changes in mEPSC amplitude.

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Animal/Disease Models: Male Wistar Han rats [1]
Doses: 50 and 250 mg/kg
Route of Administration: p.o., twice daily for 4 days
Experimental Results: Achieved dose-dependent plasma exposures, with Cmax and AUC increasing less than dose proportionally (80 and 180 %, respectively, and Tmax occurring 1-3 h post-dose. Minimal activity decreases or minimal hypoactivity were observed 2 h post-dose on days 1-3. Piloerection was observed in high-dose animals on Day 1 at 3 h post-dose. Low doses had no effect on body weight, while the high dose caused a transient 3% decrease in two animals and lower overall body weight gain in all animals. No meaningful changes were detected in globulin, protein, albumin, chloride, calcium and potassium concentrations, cholesterol level or reticulocyte count. Produced mild decreases in triglyceride levels. Showed no Olney's lesions in animals.

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Animal/Disease Models: Male Sprague-Dawley rats (8-10 weeks)[1]
Doses: 50 and 250 mg/kg
Route of Administration: p.o., twice on the same day
Experimental Results: The low dose increased heart rate and mean arterial pressure. The high dose caused a transient decrease in heart rate (associated with reduced body temperature) and an increase in blood pressure.

[1]. https://pubmed.ncbi.nlm.nih.gov/40361296/

C19H16CLF2N5O2

419.81

White to off-white solid powder

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~238.20 mM; with sonication)

配方 1 中的溶解度: ≥ 2.5 mg/mL (5.96 mM)(饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加),澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。 生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (5.96 mM)(饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加),澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中，混合均匀。 2 g SBE-β-CD（磺丁基醚 β-环糊精）粉末定容于 10 mL 的生理盐水中，完全溶解至澄清透明。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。配方 3 中的溶解度: ≥ 2.5 mg/mL (5.96 mM)(饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加),澄清溶液。
例如，若需制备1 mL的工作液，可将 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。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。