186392-40-5 Usage
Description
CP 91149 is a potent inhibitor of human liver glycogen phosphorylase a (LGPa), muscle glycogen phosphorylase a (MGPa), and MGPb, with IC50s of 0.13, 0.2, and 0.3 μM, respectively, in the presence of glucose. It is a white solid that has been found to inhibit glucagon-stimulated glycogenolysis in primary human hepatocytes and increase glycogen synthesis in rat hepatocytes. Additionally, CP 91149 inhibits brain GP and has demonstrated antitumor properties.
Uses
Used in Pharmaceutical Industry:
CP 91149 is used as an inhibitor for glycogen phosphorylase, which plays a crucial role in regulating glucose metabolism. Its inhibition can lead to growth inhibition and has potential applications in the treatment of diabetes and other glycogen metabolism-related disorders.
Used in Anticancer Applications:
CP 91149 is used as an antitumor agent, particularly effective against A549 non-small cell lung carcinoma (NSCLC) cells that express endogenous brain GP. It inhibits glycogen accumulation and proliferation in these cells, making it a promising candidate for cancer treatment.
Used in Diabetes Treatment:
In vivo studies have shown that CP 91149 can lower plasma glucose levels in diabetic ob/ob mice without causing hypoglycemia, making it a potential therapeutic agent for the treatment of diabetes.
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.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 186392-40-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,8,6,3,9 and 2 respectively; the second part has 2 digits, 4 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 186392-40:
(8*1)+(7*8)+(6*6)+(5*3)+(4*9)+(3*2)+(2*4)+(1*0)=165
165 % 10 = 5
So 186392-40-5 is a valid CAS Registry Number.
InChI:InChI=1S/C21H22ClN3O3/c1-25(2)21(28)19(26)17(10-13-6-4-3-5-7-13)24-20(27)18-12-14-11-15(22)8-9-16(14)23-18/h3-9,11-12,17,19,23,26H,10H2,1-2H3,(H,24,27)/t17-,19+/m0/s1
186392-40-5Relevant articles and documents
Use of glycogen phosphorylase inhibitors
-
, (2008/06/13)
The invention provides methods of treating prophylactically an individual in whom Type 2 diabetes mellitus has not yet presented, but in whom there is an increased risk of developing such condition, which methods comprise administering to an individual in need thereof an effective amount of a glycogen phosphorylase inhibitor; effective amounts of a glycogen phosphorylase inhibitor and a non-glycogen phosphorylase inhibiting anti-diabetic agent; or effective amounts of a glycogen phosphorylase inhibitor and an anti-obesity agent. The invention further provides methods of treating prophylactically an individual in whom Type 2 diabetes mellitus has not yet presented, but in whom there is an increased risk of developing such condition, which methods comprise administering to an individual in need thereof a pharmaceutical composition comprising effective amounts of a glycogen phosphorylase inhibitor and a non-glycogen phosphorylase inhibiting anti-diabetic agent; or effective amounts of a glycogen phosphorylase inhibitor and an anti-obesity agent.
Processes and intermediates for preparing 3(S)-[(5-chloro-1H-indole-2-carbonyl)-amino]-2(R)-hydroxy-4-phenyl-butyric acid
-
, (2008/06/13)
The present invention provides novel processes for preparing 3(S)-[(5-chloro-1H-indole-2-carbonyl)-amino]-2(R)-hydroxy-4-phenyl-butyric acid. Also provided are novel intermediates used in those processes. Further, the 3(S)-[(5-chloro-1H-indole-2-carbonyl)-amino]-2(R)-hydroxy-4-phenyl-butyric acid prepared by the novel processes can be further reacted to yield known indole 2-carboxamides and derivatives thereof possessing glycogen phosphorylase inhibitory activity, which are useful in the treatment of mammals, especially human beings, having glycogen phosphorylase dependent diseases or conditions.
Pharmaceutical compositions of glycogen phosphorylase inhibitors
-
, (2008/06/13)
Pharmaceutical compositions comprise a glycogen phosphorylase inhibitor and at least one concentration-enhancing polymer. The composition may be a simple physical mixture of glycogen phosphorylase inhibitor and concentration-enhancing polymer or a dispersion of glycogen phosphorylase inhibitor and polymer.
