SR-3306
目录号 : GC30864
SR-3306是一种有效的可渗透脑的选择性JNK抑制剂。
Cas No.:1128096-91-2
Sample solution is provided at 25 µL, 10mM.
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SR-3306 is a selective, potent, highly brain penetrant JNK inhibitor.
The effect of SR-3306 or Tat-Sab on cell viability in response to oxidative stress is measured by an MTT assay. H9c2 cells treated with 100 μM H2O2/FeSO4 are ~40% viable, whereas the addition of 500 nM SR-3306 or 500 nM SR3562 to cells treated with 100 μM H2O2/FeSO4 increases viability to ~90%, and the addition of 10 μM Tat-Sab peptide to cells treated with 100 μM H2O2/FeSO4 increases viability to ~70% compared with 98% viability in untreated cells. Similar results are found for primary human cardiomyocytes [2].
Administration of SR-3306 [10 mg/kg/day (s.c.) for 14 days] increases the number of tyrosine hydroxylase immunoreactive (TH+) neurons in the SNpc by 6-fold and reduces the loss of the TH+ terminals in the striatum relative to the corresponding side of 6-OHDA-lesioned rats that receive only vehicle (p<0.05). In addition, SR-3306 [10 mg/kg/day (s.c.) for 14 days] decreases d-amphetamine-induced circling by 87% compared to 6-hydroxydopamine (6-OHDA)-lesioned animals given vehicle. Steady-state brain levels of SR-3306 at day 14 are 347 nM, which is approximately 2-fold higher than the cell-based IC50 for this compound. Finally, immunohistochemical staining for phospho-c-jun (p-c-jun) reveals that SR-3306 [10 mg/kg/day (s.c.) for 14 days] produces a 2.3-fold reduction of the number of immunoreactive neurons in the substantia nigra pars compacta (SNpc) relative to vehicle treated rats[1]. In lean mice, intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of SR-3306 reduces food intake and body weight. Moreover, i.p. and i.c.v. administrations of SR11935 exert similar anorectic effects as SR3306, which suggests JNK2 or JNK3 mediates aspect of the anorectic effect by pan-JNK inhibition. Furthermore, daily i.p. injection of SR-3306 (7 days) prevents the increases in food intake and weight gain in lean mice upon high-fat diet feeding, and this injection paradigm reduced high-fat intake and obesity in diet-induced obese (DIO) mice[3].
[1]. Crocker CE, et al. JNK Inhibition Protects Dopamine Neurons and Provides Behavioral Improvement in a Rat 6-hydroxydopamine Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Apr 20;2(4):207-212. [2]. Chambers JW, et al. Inhibition of JNK mitochondrial localization and signaling is protective against ischemia/reperfusion injury in rats. J Biol Chem. 2013 Feb 8;288(6):4000-11. [3]. Gao S, et al. Pharmacological Inhibition of c-Jun N-terminal Kinase Reduces Food Intake and Sensitizes Leptin's Anorectic Signaling Actions. Sci Rep. 2017 Feb 6;7:41795.
Cell experiment: | H9c2 cells and primary human cardiomyocytes are grown under normal cell culture conditions (37 °C and 5% CO2) in DMEM supplemented with 10% fetal bovine serum and penicillin/streptomycin. To assure that the cells are actively growing, only cells at ~80% confluency and between passages 5 and 15 are used in our experiments. H9c2 cells and primary human cardiomyocytes are exposed to 500 nM SR-3306, 500 nM SR-3562, 0.01% DMSO vehicle control, 10 μM Tat-SabKIM1, and 10 μM Tat-scramble for 30 min prior to the addition of stress. To induce oxidative stress and mitochondrial dysfunction in H9c2 cells and primary human cardiomyocytes, 100 μM hydrogen peroxide (H2O2)/FeSO4 or 100 μM hydrogen peroxide (H2O2)/FeSO4 is added directly to the media of the cells. The cells are exposed to H2O2/FeSO4 for the times indicated in the experiments[2]. |
Animal experiment: | Rats[1]Four Sprague-Dawley rats are used. SR-3306 is dosed at 2.5 or 10 mg/kg in subcutaneous minipumps at a rate of 5 μL/h, and after 24 h on days 1, 2, 3, 4, 6, 7, 8, 9, 10, 13, and 14 blood, and day 14 brain are collected. Plasma is generated, and the samples are frozen at -80 °C. The plasma and brain are mixed with Acetonitrile (1:5 v/v or 1:5 w/v, respectively). The brain sample is sonicated with a probe tip sonicator to break up the tissue, and samples are analyzed for compound levels by LC-MS/MS. Plasma compound levels are determined against standards made in plasma and brain levels against standards made in blank brain matrix[1].Mice[3]Male, lean or DIO C57BL/6 mice are used. The mice are trained to scheduled, daily, 2-hour water access during the light for 2 weeks. On the first day of the conditioned taste aversion (CTA) test, the trained mice are given a novel 0.15% saccharin solution to drink for the first 50 minutes, and are then given an i.p. injection of SR-3306 (30 mg/kg or 60 mg/kg) or the vehicle. The injected mice are then provided water for the remaining 70 min. The next day, the mice are allowed to choose between water and 0.15% saccharin for 50 min. Fluid consumption is calculated[3]. |
References: [1]. Crocker CE, et al. JNK Inhibition Protects Dopamine Neurons and Provides Behavioral Improvement in a Rat 6-hydroxydopamine Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Apr 20;2(4):207-212. | |
| Cas No. | 1128096-91-2 | SDF | |
| Canonical SMILES | CC(C=C1)=NC=C1C2=NN(C=N2)C3=CC=C(NC4=NC=CC(C5=CC=CC(N6CCOCC6)=C5)=N4)C=C3 | ||
| 分子式 | C28H26N8O | 分子量 | 490.56 |
| 溶解度 | DMSO : 125 mg/mL (254.81 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0385 mL | 10.1924 mL | 20.3849 mL |
| 5 mM | 0.4077 mL | 2.0385 mL | 4.077 mL |
| 10 mM | 0.2038 mL | 1.0192 mL | 2.0385 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet