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受注：045-509-1970 |
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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 |
| 化学式 | C23H21FN6O |
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| 分子量 | 416.45 | CAS No. | 1337532-29-2 | |
| Solubility (25°C)* | 体外 | DMSO | 20 mg/mL (48.02 mM) | |
| Ethanol | 10 mg/mL (24.01 mM) | |||
| Water | Insoluble | |||
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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 | GSK2656157 is an ATP-competitive and highly selective inhibitor of PERK with IC50 of 0.9 nM in a cell-free assay, 500-fold greater against a panel of 300 kinases. GSK2656157 decreases apoptosis and inhibits excessive autophagy. |
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| in vitro | Pretreatment of cells with GSK2656157 results in inhibition of PERK activation as well as decreases in the downstream substrates, phospho-eIF2a, ATF4, and CHOP with an IC50 in the range of 10-30 nM. Cells that are exposed to 1 mM GSK2656157 before UPR induction are able to block this effect on de novo protein synthesis. Five of 84 UPR-related genes (DDIT3, HERPUD1, PPP1R15A, C/EBP-beta, and ERN1) are down regulated more than 4-fold by GSK2656157. In the absence of exogeneous UPR inducers, GSK2656157 has no significant effect on the growth of any of these cells with IC50 range of 6–25 mM. Thus, GSK2656157 can be used to evaluate the biologic function of PERK in various biologic contexts. [1] |
| in vivo | Complete inhibition of phospho-PERK Thr980 is observed through 8 hours after a single 50 mg/kg oral dose of GSK2656157. Treatment of mice with 50 or 150 mg/kg twice daily dosing of GSK2656157 results in dose-dependent inhibition of tumor growth in four models; reaching 54–114% tumor growth inhibition at the 150 mg/kg, twice daily dose. Altered amino acid metabolism, decreased blood vessel density, and vascular perfusion are potential mechanisms for the observed antitumor effect. Treatment of mice with GSK2656157 results in inhibition of tumor growth in multiple human tumor xenografts. [1] |
| 特徴 | Orally bioavailable PERK-selective inhibitor that functions independent of eIF2α phosphorylation. |
プロトコル(参考用のみ)
| キナーゼアッセイ | Kinase assay | |
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| Inhibitory potency of GSK2656157 is measured using recombinant GST-PERK (536–1116 amino acids) with 6-His-full-length human eIF2a as a substrate. Kinase selectivity is evaluated using 27 kinases at GSK as well as a panel of 300 kinases. | ||
| 細胞アッセイ | 細胞株 | human tumor cell lines, primary human microvascular endothelial cells |
| 濃度 | ~3 μM | |
| 反応時間 | 3 day | |
| 実験の流れ | Antiproliferative activity of GSK2656157 against multiple human tumor cell lines as well as primary human microvascular endothelial cells is evaluated in a 3-day proliferation assay using standard culture medium. In the absence of exogeneous UPR inducers, GSK2656157 has no significant effect on the growth of any of these cells with IC50 range of 6–25 mM. |
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| 動物実験 | 動物モデル | human tumor xenograft models |
| 投薬量 | 50 or 150 mg/kg, twice daily | |
| 投与方法 | Orally | |
カスタマーフィードバック
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Data from [Data independently produced by , , Cell Res, 2015, 25: 946-962]
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Data from [Data independently produced by , , Neurotox Res, 2017, 31(2):218-229.]
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：
| Mannose metabolism inhibition sensitizes acute myeloid leukaemia cells to therapy by driving ferroptotic cell death [ Nat Commun, 2023, 14(1):2132] | PubMed: 37059720 |
| Loss of PERK function promotes ferroptosis by downregulating SLC7A11 (System Xc⁻) in colorectal cancer [ Redox Biol, 2023, 65:102833] | PubMed: 37536085 |
| A program of successive gene expression in mouse one-cell embryos [ Cell Rep, 2023, 42(2):112023] | PubMed: 36729835 |
| Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet β cells in mice [ J Transl Med, 2023, 21(1):89] | PubMed: 36747238 |
| Acute Endoplasmic Reticulum Stress Suppresses Hepatic Gluconeogenesis by Stimulating MAPK Phosphatase 3 Degradation [ Int J Mol Sci, 2023, 24(21)15561] | PubMed: 37958545 |
| Rilotumumab Resistance Acquired by Intracrine Hepatocyte Growth Factor Signaling [ Cancers (Basel), 2023, 15(2)460] | PubMed: 36672409 |
| PERK arm of UPR selectively regulates ferroptosis in colon cancer cells by modulating the expression of SLC7A11 (System Xc-) [ bioRxiv, 2023, 10.1101/2023.03.28.534659] | PubMed: none |
| PERK is a critical metabolic hub for immunosuppressive function in macrophages [ Nat Immunol, 2022, 23(3):431-445] | PubMed: 35228694 |
| A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis [ Nat Cell Biol, 2022, 24(5):766-782] | PubMed: 35501370 |
| Scleral PERK and ATF6 as targets of myopic axial elongation of mouse eyes [ Nat Commun, 2022, 13(1):5859] | PubMed: 36216837 |
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。