CP-91149 is a small-molecule glycogen phosphorylase (GP) inhibitor developed to investigate hepatic glycogen breakdown as a target for lowering blood glucose. GP releases glucose-1-phosphate from glycogen, supplying a precursor for hepatic glucose production.
The CP-91149 chemical structure combines a 5-chloroindole-2-carboxamide core with a hydroxylated side chain containing a benzyl group and an N,N-dimethylamide. Its molecular formula is C21H22ClN3O3.
Application of CP-91149
In metabolic research, the compound helps assess how glycogenolysis contributes to glucose output and glycogen storage. Measuring glucose release alongside glycogen content is useful for distinguishing reduced breakdown from changes in synthesis.
It also supports studies of glycogen metabolism in proliferating cells. Growth inhibition has been reported in both cancer cells and normal fibroblasts, so sensitivity should be evaluated against GP expression rather than assumed to be tumour-specific.
In Vitro
Human liver GPa was inhibited with an IC50 of 0.13 µM at 7.5 mM glucose. In primary human hepatocytes, the IC50 for glucagon-stimulated glycogenolysis was 2.1 µM; this cellular endpoint should be distinguished from purified-enzyme potency.
A549 lung carcinoma cells accumulated glycogen and showed slower growth after treatment. Normal HSF55 fibroblasts also accumulated glycogen and underwent G1 arrest. These findings support parallel measurements of glycogen, proliferation and viability.
The CP-91149 molecular weight is 399.87 g/mol for calculating molar stock concentrations. Confirm solvent compatibility and dilution behaviour using the supplied material’s documentation.
In Vivo
Oral studies with the Pfizer CP-91149 compound in diabetic ob/ob mice showed glucose reductions of 100–120 mg/dL within three hours at 25–50 mg/kg. Hypoglycaemia was not observed, and glucose was not lowered in normoglycaemic controls under the conditions tested.
In non-fasted Goto-Kakizaki rats, combination with the fructose-1,6-bisphosphatase inhibitor CS-917 limited hepatic glycogen depletion and lowered plasma glucose more than CS-917 alone.
Biochemical and Physiological Actions
The CP-91149 molecular structure provides an indole-based framework for allosteric GP inhibition. Potency is 5- to 10-fold lower without glucose, making glucose concentration an important assay variable. This dependence does not establish protection against hypoglycaemia across models or dosing regimens.
GP inactivation can also promote glycogen synthase activation. In hepatocyte experiments, glycogen synthesis increased sevenfold at 5 mM glucose and twofold at 20 mM, illustrating how inhibiting breakdown can shift metabolism towards storage.
Features and Benefits of CP-91149
The compound offers enzyme, cellular and oral animal data for comparing GP inhibition across experimental settings. Match CAS 186392-40-5 to the intended reference material.
The CP-91149 structure contains two stereocentres. Confirming stereochemistry and analytical identity helps make comparisons between batches and related inhibitors meaningful.
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