CP-91149
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.
| Storage | Store at -20°C |
| M.Wt | 399.87 |
| Cas No. | 186392-40-5 |
| Formula | C21H22ClN3O3 |
| Solubility | insoluble in H2O; ≥16.4 mg/mL in DMSO; ≥3.17 mg/mL in EtOH with ultrasonic |
| Chemical Name | 5-chloro-N-[(2S,3R)-4-(dimethylamino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl]-1H-indole-2-carboxamide |
| SDF | Download SDF |
| Canonical SMILES | CN(C)C(=O)C(C(CC1=CC=CC=C1)NC(=O)C2=CC3=C(N2)C=CC(=C3)Cl)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| 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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| Description | CP-91149 is a selective inhibitor of glycogen phosphorylase (GP) with an IC50 value of 0.13 μM. | |||||
| Targets | GP | |||||
| IC50 | 0.13 μM | |||||
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