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受注：045-509-1970 |
技術サポート：tech@selleck.co.jp 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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| 化学式 | C21H22ClN3O3 |
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| 分子量 | 399.87 | CAS No. | 186392-40-5 | ||||
| Solubility (25°C)* | 体外 | DMSO | 80 mg/mL (200.06 mM) | ||||
| Water | Insoluble | ||||||
| Ethanol | Insoluble | ||||||
| 体内 （毎回新しく調製した物を用意してください） |
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | CP-91149は、選択的グリコーゲンホスホリラーゼ（GP）阻害剤であり、グルコース存在下でのIC50は0.13 μMです。グルコース非存在下では、5〜10倍効力が低下します。 |
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| in vitro | CP-91149 displays 200-fold higher inhibitory activity against human liver glycogen phosphorylase a (HLGPa) than caffeine (IC50 = 26 μM). This compound (10-100 μM) inhibits -stimulated glycogenolysis in isolated rat hepatocytes in a dose-dependent manner, and in primary human hepatocytes with IC50 of ~2.1 μM. It also potently inhibits the activities of human muscle phosphorylase a and b with IC50 of 0.2 μM and ~0.3 μM, respectively. Treatment with this chemical 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. It can partially counteract the effects of phosphorylase overexpression. This compound also potently inhibits brain GP with IC50 of 0.5 μM in A549 cells. Treatment at 10-30 μM causes significant glycogen accumulation in A549 and HSF55 cells. It 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. This chemical 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. |
| 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. This compound treatment does not lower glucose levels in normoglycemic, nondiabetic mice. In the non-fasted Goto-Kakizaki (GK) rats, administration of this chemical in combination with CS-917 suppresses hepatic glycogen reduction by CS-917 and decreases plasma glucose more than single administration of CS-917. |
プロトコル(参考用のみ)
| キナーゼアッセイ | Phosphorylase enzyme assay | |
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| 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 this compound are added to the assay in 5 μL of 14% DMSO. | ||
| 細胞アッセイ | 細胞株 | HSF55 and T98G |
| 濃度 | Dissolved in DMSO, final concentrations ~50 μM | |
| 反応時間 | 72 hours | |
| 実験の流れ | 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. |
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| 動物実験 | 動物モデル | Obese, diabetic male C57BL/6J-Lep(ob/ob) mice and their lean, nondiabetic C57BL/6J-/+ littermates |
| 投薬量 | ~50 mg/kg | |
| 投与方法 | Orally | |
参考
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カスタマーフィードバック
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, , Mol Cancer Res, 2014, 12(11):1547-59.
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| Regulation of stress granule formation in human oligodendrocytes [ Nat Commun, 2024, 15(1):1524] | PubMed: 38374028 |
| Glycogenesis and glyconeogenesis from glutamine, lactate and glycerol support human macrophage functions [ EMBO Rep, 2024, 10.1038/s44319-024-00278-4] | PubMed: 39424955 |
| Mutant IDH regulates glycogen metabolism from early cartilage development to malignant chondrosarcoma formation [ Cell Rep, 2023, 42(6):112578] | PubMed: 37267108 |
| Glycogen phosphorylase inhibition alongside taxol chemotherapy synergistically elicits ferroptotic cell death in clear cell ovarian and kidney cancers [ bioRxiv, 2023, 10.1101/2023.05.01.538916] | PubMed: None |
| 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 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。