CP-91149
(Synonyms: 5-氯-N-[(1S,2R)-3-(二甲基氨基)-2-羟基-3-氧代-1-(苯基甲基)丙基]-1H-吲哚-2-甲酰胺) 目录号 : GC16418
A glycogen phosphorylase inhibitor
Cas No.:186392-40-5
Sample solution is provided at 25 µL, 10mM.
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CP-91149 is a selective inhibitor of glycogen phosphorylase (GP) with an IC50 value of 0.13 μM.
Glycogen phosphorylase is a phosphorylase enzymes that can catalize phosphorolytic cleavage of the glycosidic linkages of glycogen by releasing glucose-1-phosphate from the terminal alpha-1, 4-glycosidic bond. It controls the rate-limiting step in glycogenolysis in the cells.
In vitro, CP-91149 treatment suppressed glycogenolysis stimulated by glucagon in in primary human hepatocytes and isolated rat hepatocytes with IC50 value of 2.1 μM and 10–100 μM, respectively 1. Inhibition of phosphorylase a by CP-91149 resulted in activation of glycogen synthase and translocation of the protein from a soluble to a particulate fraction, which mimicked the insulin- stimulated glycogen synthesis 2.
In vivo, treatment of CP-91149 on diabetic ob/ob mice at a dosage of 25–50 mg/kg was shown to lead to a rapid glucose lowering but did not change glucose levels in normoglycemic, nondiabetic mice 1.
References:
1. Martin WH, Hoover DJ, Armento SJ, et al. Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(4):1776-1781.
2. Aiston S, Coghlan MP, Agius L. Inactivation of phosphorylase is a major component of the mechanism by which insulin stimulates hepatic glycogen synthesis. European journal of biochemistry / FEBS. 2003;270(13):2773-2781.
| Cell experiment [1]: | |
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Cell lines |
Hepatocytes from the liver of male Wistar rats. |
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Preparation method |
The solubility of this compound in DMSO﹥16.4mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
2.5μm for 3h. |
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Applications |
CP-91149 could inhibit phosphorylase potently and selectively which caused conversion of phosphorylase a to b in hepatocytes. Stimulation of glycogen synthesis by CP-91149 was due to dephosphorylation of phosphorylase a rather than inhibition of glycogen degradation or cycling. |
| Animal experiment [2]: | |
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Animal models |
Diabetic male C57BL/6J-Lep(ob/ob) mice |
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Dosage form |
oral dose of CP-91149 at 10, 25, and 50 mg/kg(effective at the latter two concentration) |
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Application |
In the diabetic male C57BL/6J-Lep(ob/ob) mice, glucose lowering by CP-91149 was statistically significant and it reached normoglycemia at 50 mg/kg. It could inhibit hepatic glycogenolysis and lower plasma glucose levels. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Aiston S, Coghlan MP, Agius L. Inactivation of phosphorylase is a major component of the mechanism by which insulin stimulates hepatic glycogen synthesis. European journal of biochemistry / FEBS. 2003;270(13):2773-2781. [2] Martin WH, Hoover DJ, Armento SJ, et al. Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(4):1776-1781. |
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| Cas No. | 186392-40-5 | SDF | |
| 别名 | 5-氯-N-[(1S,2R)-3-(二甲基氨基)-2-羟基-3-氧代-1-(苯基甲基)丙基]-1H-吲哚-2-甲酰胺 | ||
| 化学名 | 5-chloro-N-[(2S,3R)-4-(dimethylamino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl]-1H-indole-2-carboxamide | ||
| Canonical SMILES | CN(C)C(=O)C(C(CC1=CC=CC=C1)NC(=O)C2=CC3=C(N2)C=CC(=C3)Cl)O | ||
| 分子式 | C21H22ClN3O3 | 分子量 | 399.87 |
| 溶解度 | 25 mg/ml in DMSO, 25 mg/ml in DMF | 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 | 2.5008 mL | 12.5041 mL | 25.0081 mL |
| 5 mM | 0.5002 mL | 2.5008 mL | 5.0016 mL |
| 10 mM | 0.2501 mL | 1.2504 mL | 2.5008 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