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| | CP 91149 Basic information |
| | CP 91149 Chemical Properties |
| Melting point | 190-192°C | | storage temp. | 2-8°C | | solubility | DMSO: >20mg/mL | | form | powder | | color | white to off-white | | Stability: | Hygroscopic |
| Hazard Codes | Xn | | Risk Statements | 22 | | WGK Germany | 3 |
| | CP 91149 Usage And Synthesis |
| Description | CP 91,149 is an inhibitor of human liver glycogen phosphorylase a (LGPa), muscle glycogen phosphorylase a (MGPa), and MGPb (IC50s = 0.13, 0.2, and 0.3 μM, respectively, in the presence of glucose). CP 91,149 is 5- to 10-fold less potent in the absence of glucose. In vitro, it inhibits glucagon-stimulated glycogenolysis in primary human hepatocytes (IC50 = 2.1 μM) and increases glycogen synthesis in rat hepatocytes at a concentration of 2.5 μM in the presence of 5 mM glucose. CP 91,149 inhibits brain GP (IC50 = 0.5 μM) and, at a concentration of 30 μM, inhibits glycogen accumulation and proliferation of A549 non-small cell lung carcinoma (NSCLC) cells that express endogenous brain GP. In vivo, CP 91,149 (25 mg/kg, p.o.) lowers the plasma glucose level in diabetic ob/ob mice within 3 hours of administration without producing hypoglycemia, but has no effect on normoglycemic, non-diabetic mice. | | Chemical Properties | White Solid | | Uses | Inhibition of glycogen phosphorylase (GP) by CP-91,149 induces growth inhibition correlating with brain GP expression. Antitumor agent.
| | Biochem/physiol Actions | CP-91149 is a selective glycogen phosphorylase inhibitor. | | 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. | | target | GP | | 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. |
| | CP 91149 Preparation Products And Raw materials |
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