GSK1059865
目录号 : GC30832
GSK1059865是有效地食欲素1受体(orexin1receptor)拮抗剂。
Cas No.:1191044-58-2
Sample solution is provided at 25 µL, 10mM.
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GSK1059865 is a potent orexin 1 receptor antagonist.
Treatment with GSK1059865 significantly decreases ethanol drinking in a dose-dependent manner in CIE-exposed mice. In contrast GSK1059865 decreases drinking in air-exposed mice only at the highest dose used. There is no effect of GSK1059865 on sucrose intake[1]. GSK1059865 (0.3 nM-10 nM) produces non-surmountable antagonism with a dose-dependent rightward shift of the OXA EC50 and a concomitant decrease of the agonist maximal response. The calculated pKB value is 8.77±0.12 for GSK1059865. GSK1059865 (0.1-3.3 μM) produces a classical surmountable profile with parallel rightward shift of the OXA EC50 without depression of the agonist maximal response[2]. Intraperitoneal administration of GSK1059865 produces a region-dependent inhibition of yohimbine-induced relative cerebral blood volume response. The administration of GSK1059865 per se produces a weak relative cerebral blood volume increase in several brain regions. GSK1059865-pretreated animals exhibit slightly higher baseline mean arterial blood pressure values than controls[3].
[1]. Lopez MF, et al. The highly selective orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol drinking in ethanol dependent mice. Brain Res. 2016 Apr 1;1636:74-80. [2]. Piccoli L, et al. Role of orexin-1 receptor mechanisms on compulsive food consumption in a model of binge eating in female rats. Neuropsychopharmacology. 2012 Aug;37(9):1999-2011. [3]. Gozzi A, et al. Differential effect of orexin-1 and CRF-1 antagonism on stress circuits: a fMRI study in the rat with the pharmacological stressor Yohimbine. Neuropsychopharmacology. 2013 Oct;38(11):2120-30.
Animal experiment: | Rats: GSK1059865 is dissolved in 0.5% HPMC (w/v) in distilled water and administered by gavage at doses of 10 and 30 mg/kg to rats. Drug or vehicle is administered 1 h before access to highly palatable food[2]. Mice: During baseline and the first 5 test cycles following chronic intermittent ethanol (or air) exposure, mice receive vehicle (saline) injections (i.p.; 0.01 ml/g body weight) 30 minutes before drinking ethanol. On test cycles 6 and 7 mice receive vehicle or GSK1059865 (10, 25, 50 mg/kg) before given access to ethanol 15% v/v (Test 6) or sucrose 5% w/v (Test 7) versus water. GSK1059865 is dissolved in saline and TWEEN 80 (0.5 % v/v) as vehicle[1]. |
References: [1]. Lopez MF, et al. The highly selective orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol drinking in ethanol dependent mice. Brain Res. 2016 Apr 1;1636:74-80. | |
| Cas No. | 1191044-58-2 | SDF | |
| Canonical SMILES | O=C(N1[C@H](CNC2=NC=C(Br)C=C2)CC[C@H](C)C1)C3=CC=CC(F)=C3OC | ||
| 分子式 | C20H23BrFN3O2 | 分子量 | 436.32 |
| 溶解度 | DMSO : ≥ 50 mg/mL (114.59 mM) | 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 | 2.2919 mL | 11.4595 mL | 22.919 mL |
| 5 mM | 0.4584 mL | 2.2919 mL | 4.5838 mL |
| 10 mM | 0.2292 mL | 1.1459 mL | 2.2919 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
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet