CP-91149

Catalog No.S2717 Batch:S271750

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Technical Data

Formula

C21H22ClN3O3
Molecular Weight 399.87 CAS No. 186392-40-5
Solubility (25°C)* In vitro DMSO 80 mg/mL (200.06 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
0.5% methylcellulose 0.2% Tween 80
5.0mg/ml Taking the 1 mL working solution as an example, take 5 mg of this product and add it to 1 ml of 0.5% methylcellulose+0.2% Tween 80 clear solution, and mix evenly to form a uniform suspension. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description CP-91149 is a selective glycogen phosphorylase (GP) inhibitor with IC50 of 0.13 μM in the presence of glucose, 5- to 10-fold less potent in the absence of glucose.
Targets
Glycogen phosphorylase (GP) [1]
0.13 μM
In vitro CP-91149 displays 200-fold higher inhibitory activity against human liver glycogen phosphorylase a (HLGPa) than caffeine (IC50 = 26 μM). CP-91149 (10-100 μM) inhibits glucagon-stimulated glycogenolysis in isolated rat hepatocytes in a dose-dependent manner, and in primary human hepatocytes with IC50 of ~2.1 μM. [1] CP-91149 also potently inhibits the activities of human muscle phosphorylase a and b with IC50 of 0.2 μM and ~0.3 μM, respectively. CP-91149 treatment at 2.5 μM induces inactivation of phosphorylase and sequential activation of glycogen synthase in hepatocytes, and increases glycogen synthesis by 7-fold at 5 mM glucose and by 2-fold at 20 mM glucose. CP-91149 can partially counteract the effects of phosphorylase overexpression. [2] CP-91149 also potently inhibits brain GP with IC50 of 0.5 μM in A549 cells. CP-91149 treatment at 10-30 μM causes significant glycogen accumulation in A549 and HSF55 cells. CP-91149 treatment increases G1-phase cells with a significant reduction of the S-phase population in HSF55 cells, correlated with increased expression of p21 and p27. [3] CP-91149 also promotes the dephosphorylation and activation of GS (glycogen synthase) in non-engineered or GP-overexpressing cultured human muscle cells, but exclusively in glucose-deprived cells. [4]
In vivo Oral administration of CP-91149 to diabetic ob/ob mice at 25-50 mg/kg causes rapid (3 hours) glucose lowering by 100-120 mg/dl without producing hypoglycemia, resulting from inhibition of glycogenolysis in vivo. CP-91149 treatment does not lower glucose levels in normoglycemic, nondiabetic mice. [1] In the non-fasted Goto-Kakizaki (GK) rats, administration of CP-91149 in combination with CS-917 suppresses hepatic glycogen reduction by CS-917 and decreases plasma glucose more than single administration of CS-917. [5]

Protocol (from reference)

Kinase Assay:[1]
  • Phosphorylase enzyme assay

    Human liver glycogen phosphorylase a (HLGPa, 85 ng) activity is measured in the direction of glycogen synthesis by the release of phosphate from glucose-1-phosphate at 22°C in 100 μL of buffer containing 50 mM Hepes (pH 7.2), 100 mM KCl, 2.5 mM EGTA, 2.5 mM MgCl2, 0.5 mM glucose-1-phosphate, and 1 mg/mL glycogen. Phosphate is measured at 620 nm, 20 minutes after the addition of 150 μL of 1 M HCl containing 10 mg/mL ammonium molybdate and 0.38 mg/mL malachite green. Increasing concentrations of CP-91149 are added to the assay in 5 μL of 14% DMSO.
Cell Assay:[3]
  • Cell lines

    HSF55 and T98G

  • Concentrations

    Dissolved in DMSO, final concentrations ~50 μM

  • Incubation Time

    72 hours

  • Method

    Cells are exposed to various concentrations of CP-91149 for 72hours. Viability is determined with manual cell counts following staining with trypan blue exclusion assay. Cells are fixed with 70% ethanol. DNA is stained with propidium iodide and the intensity of fluorescence is measured using a Becton-Dickinson flow cytometer at 488nm for excitation and at 650nm for emission. The cell cycle profile is analyzed using Modifit's Sync Wizard.
Animal Study:[1]
  • Animal Models

    Obese, diabetic male C57BL/6J-Lep(ob/ob) mice and their lean, nondiabetic C57BL/6J-/+ littermates

  • Dosages

    ~50 mg/kg

  • Administration

    Orally

Customer Product Validation

, , Mol Cancer Res, 2014, 12(11):1547-59.

Selleck's CP-91149 has been cited by 11 publications

Regulation of stress granule formation in human oligodendrocytes [ Nat Commun, 2024, 15(1):1524] PubMed: 38374028
Mutant IDH regulates glycogen metabolism from early cartilage development to malignant chondrosarcoma formation [ Cell Rep, 2023, 42(6):112578] PubMed: 37267108
Intracellular energy controls dynamics of stress-induced ribonucleoprotein granules [ Nat Commun, 2022, 13(1):5584] PubMed: 36151083
Intracellular energy controls dynamics of stress-induced ribonucleoprotein granules [ Nat Commun, 2022, 13(1):5584] PubMed: 36151083
TCR activation directly stimulates PYGB-dependent glycogenolysis to fuel the early recall response in CD8+ memory T cells [ Mol Cell, 2022, S1097-2765(22)00538-X] PubMed: 35738262
A genome-wide CRISPR-Cas9 screen identifies CENPJ as a host regulator of altered microtubule organization during Plasmodium liver infection [ Cell Chem Biol, 2022, S2451-9456(22)00205-7] PubMed: 35738280
Analysis of the expression, function and signaling of glycogen phosphorylase isoforms in hepatocellular carcinoma [ Oncol Lett, 2022, 24(2):244] PubMed: 35761940
Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists. [ Cells, 2020, 9(3)] PubMed: 32183271
Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists [ Cells, 2020, 9(3)E715] PubMed: 32183271
Lactate production is a prioritized feature of adipocyte metabolism. [ J Biol Chem, 2020, 295(1):83-98] PubMed: 31690627

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.