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Synonyms | compound 1 | Storage (From the date of receipt) |
3 years -20°C powder | |
化学式 | C28H31N7O3 |
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分子量 | 513.59 | CAS No. | 1893397-65-3 | |
Solubility (25°C)* | 体外 | DMSO | 10 mg/mL (19.47 mM) | |
Water | ˂1 mg/mL | |||
Ethanol | ˂1 mg/mL | |||
* <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 | TBK1/IKKε-IN-5 (compound 1) is a dual inhibitor of TANK-binding kinase 1 (TBK1) and IκB kinase-ε (IKKε/IKK-i) with IC50 of 1.0 nM and 5.6 nM for TBK1 and IKKε, respectively. TBK1/IKKε inhibition enhances response to PD-1 blockade, which effectively predicts tumor response in vivo. |
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in vitro | TBK1/IKKε-IN-5(compound 1) effectively blocks immune suppressive cytokine elaboration by CT26 cell line spheroids, without cytotoxic effects, and enhances secretion of IL-2 and IFN-γ from purified CD4+ and CD8+ T cells from healthy human donors and IL-2 from Jurkat human T-cell leukemia cells. Ex vivo addition of TBK1/IKKε-IN-1(compound 1) to PD-1 blockade enhances killing of CT26 MDOTS, associated with decreased levels of CCL4, CCL3, and IL-1β and induction of cytokines involved in activated innate immune responses.[1] |
in vivo | Balb/c mice bearing CT26 tumors are treated with TBK1/IKKε-IN-1(compound 1) ± anti-PD-L1. Consistent with MDOTS profiling data, greater tumor control and longer survival is evident with TBK1/IKKε-IN-1(compound 1) + anti-PD-L1 than with either TBK1/IKKε-IN-1(compound 1) or anti-PD-L1 alone. Reimplantation of CT26 into mice with exceptional responses to combination therapy shows no growth, whereas EMT-6 implanted tumors grow normally, suggesting induction of immunologic memory of CT26 cells in mice treated with TBK1/IKKε-IN-1(compound 1) + anti-PD-L1. Therefore, MDOTS profiling effectively recapitulates the in vivo response to PD-1 blockade +/− TBK1/IKKε inhibition, highlighting the potential of ex vivo screening in MDOTS to develop combination immunotherapies.[1] |
細胞アッセイ | 細胞株 | HCT116 cells, human CD4+ T cells, human CD8+ T cells |
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濃度 | 1 μM | |
反応時間 | 1 h, 24 h, 96 h | |
実験の流れ | Interleukin-2 and interferon gamma analysis—Freshly isolated human CD4+ and CD8+ T cells are spun down and resuspended in serum free X-vivo15 media supplemented with 5 ng/mL IL-17 and incubated overnight at 37°C. Cells are plated on anti-CD3 coated plates with 2 μg/mL anti-CD28. Cells are treated in replicate plates with a dose-titration of TBK1/IKKε-IN-1(compound 1) for 24 hours for IL-2 and 96 hours for IFNγ. IL-2 and IFNγ in the supernatant are measured using single-or multi-plex immunoassay. Jurkat T cell leukemia cells plated on anti-CD3 coated plates are treated with a dose titration of TBK1/IKKε-IN-1(compound 1) for 24 hours. |
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動物実験 | 動物モデル | 11-12 week old female Balb/c mice implanted with 1×106 CT26 colon carcinoma cells. |
投薬量 | 40 mg/kg | |
投与方法 | Oral gavage |
Atypical inflammatory kinase IKBKE phosphorylates and inactivates FoxA1 to promote liver tumorigenesis [ Sci Adv, 2024, 10(6):eadk2285] | PubMed: 38324694 |
Circadian regulator CLOCK promotes tumor angiogenesis in glioblastoma [ Cell Rep, 2023, 42(2):112127] | PubMed: 36795563 |
Identification of Natural Products Inhibiting SARS-CoV-2 by Targeting Viral Proteases: A Combined in Silico and in Vitro Approach [ J Nat Prod, 2023, acs.jnatprod.2c00843] | PubMed: 36651644 |
IKBKE phosphorylates and stabilizes Snail to promote breast cancer invasion and metastasis [ Cell Death Differ, 2022, 10.1038/s41418-022-00940-1] | PubMed: 35066576 |
Pharmacological Inhibition of IKK to Tackle Latency and Hyperinflammation in Chronic HIV-1 Infection [ Int J Mol Sci, 2022, 23(23)15000] | PubMed: 36499329 |
Structural Modification of Natural Product Tanshinone I Leading to Discovery of Novel Nitrogen-Enriched Derivatives with Enhanced Anticancer Profile and Improved Drug-like Properties [ J Med Chem, 2018, 61(3):760-776] | PubMed: 29294282 |
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。