受注:045-509-1970 |
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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 | C17H20N6O2 |
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分子量 | 340.38 | CAS No. | 1849590-01-7 | ||||||||
Solubility (25°C)* | 体外 | DMSO | 13 mg/mL (38.19 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. |
製品説明 | Tomivosertib (eFT-508) is a potent and selective MNK1/2 inhibitor with IC50s of 2.4 nM and 1 nM, respectively. It potentially results in decreased tumor cell proliferation and tumor growth. Tomivosertib (eFT-508) inhibits eIF4E phosphorylation and dramatically downregulates PD-L1 protein abundance. |
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in vitro | eFT508 has a half-maximal inhibitory concentration (IC50) of 1-2 nM against both MNK isoforms in enzyme assays and inhibits the kinase through a reversible, ATP-competitive mechanism of action. Treatment of tumor cell lines with eFT508 leads to a dose-dependent reduction in eIF4E phosphorylation at serine 209 (IC50 = 2-16 nM). In a panel of ~50 hematological cancers, eFT508 shows anti-proliferative activity against multiple DLBCL cell lines. Sensitivity to eFT508 in TMD8, OCI-Ly3 and HBL1 DLBCL cell lines is associated with dose-dependent decreases in production of pro-inflammatory cytokines including TNFα, IL-6, IL-10 and CXCL10[1]. |
in vivo | eFT508 is well-tolerated and shows efficacy against MyD88-mutant DLBCL models in vivo. Significant anti-tumor activity of eFT508 is observed in the TMD8 and HBL-1 ABC-DLBCL models(subcutaneous human lymphoma xenograft models), both of which harbor activating MyD88 mutations[1]. |
細胞アッセイ | 細胞株 | TMD8 cells |
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濃度 | 0.01, 0.1, 1, 3, 10 μM | |
反応時間 | 24 h | |
実験の流れ | TMD8 cells are treated with the indicated concentrations of eFT508 for 24 h. Cell lysates are subjected to m7-GTP Sepharose pull-down and bound proteins are analyzed by immunoblotting with the indicated antibodies. |
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動物実験 | 動物モデル | TMD8 xenograft bearing animals |
投薬量 | 1 mg/kg or 10 mg/kg | |
投与方法 | p.o. |
Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy [ PLoS Biol, 2023, 21(8):e3002227] | PubMed: 37531320 |
MAPK-interacting kinases inhibition by eFT508 overcomes chemoresistance in preclinical model of osteosarcoma [ Hum Exp Toxicol, 2023, 42:9603271231158047] | PubMed: 36840478 |
Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers [ JCI Insight, 2022, 7(22e158060)] | PubMed: 36256477 |
Treatment with eFT-508 increases chemosensitivity in breast cancer cells by modulating the tumor microenvironment [ J Transl Med, 2022, 20(1):276] | PubMed: 35717238 |
Overcoming Paradoxical Kinase Priming by a Novel MNK1 Inhibitor [ J Med Chem, 2022, 10.1021/acs.jmedchem.1c01941] | PubMed: 35417652 |
Inhibition MNK-eIF4E-β-catenin preferentially sensitizes gastric cancer to chemotherapy [ Fundam Clin Pharmacol, 2022, 10.1111/fcp.12759] | PubMed: 35048413 |
Inhibiting the MNK1/2-eIF4E axis impairs melanoma phenotype switching and potentiates anti-tumor immune responses [ J Clin Invest, 2021, 140752] | PubMed: 33690225 |
Overcoming Adaptive Resistance to KRAS and MEK Inhibitors by Co-targeting mTORC1/2 Complexes in Pancreatic Cancer [ Cell Rep Med, 2020, 1(8):100131] | PubMed: 33294856 |
eIF4E S209 phosphorylation licenses myc- and stress-driven oncogenesis [ Elife, 2020, 9e60151] | PubMed: 33135632 |
Inhibition of Growth of TSC2-Null Cells by a PI3K/mTOR Inhibitor but Not by a Selective MNK1/2 Inhibitor. [ Biomolecules, 2019, 10(1)] | PubMed: 31878201 |
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。