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Formula | C28H31N7O3 |
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Molecular Weight | 513.59 | CAS No. | 1893397-65-3 | ||||
Solubility (25°C)* | In vitro | DMSO | 5 mg/mL (9.73 mM) | ||||
Water | Insoluble | ||||||
Ethanol | Insoluble | ||||||
In vivo (Add solvents to the product individually and in order) |
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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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | 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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Targets |
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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] |
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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] |
Cell Assay: |
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Animal Study: |
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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 |
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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.