T6167923 (C09-1182-284)

T6167923 is a selective inhibitor of MyD88-dependent signaling pathways. T6167923 directly binds to Toll/IL1 receptor (TIR) domain of MyD88 and disrupts MyD88 homodimeric formation. T6167923 inhibits NF-κB driven Staphylococcus enterotoxin AP (SEAP) activity, and improves anti-inflammatory activity with IC 50 s of 2.7  μM, 2.9 μM, 2.66 μM and 2.66 μM for IFN-γ , IL-1β, IL-6 and TNF-α, respectivelyIn VitroT6167923 (0-500 μM; 20 h) inhibits the pro-inflammatory cytokine response of staphylococcal enterotoxin B (SEB) in peripheral blood mono nuclear cells. T6167923 (10-500 μM; 2 h) inhibits secreted alkaline phosphatase response (SEAP) expression in HEK 293T cells. T6167923 (100 μM; 16 h) binds to TIR protein and reduced the inhibitory effect on MyD88-signaling. T6167923 (1-500 μM; 13 h) inhibits full-length MyD88 homodimeric formation. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: Peripheral blood mono nuclear cells Concentration: 0-500 μM Incubation Time: 20 hours Result: Dose-dependently attenuated the response of SEB to TNF-α, INF-γ, IL-6, and IL-1β with IC 50 s of 2.66, 2.7, 2.66 and 2.9 μM in peripheral blood mono nuclear cells. Cell Viability AssayCell Line: HEK 293T cell line Concentration: 10-500 μM Incubation Time: 2 hours Result: Dose-dependently inhibited lipo-polysaccharide (LPS) induced MyD88-mediated NF-kB driven SEAP expression in HEK 293T cells with IC 50 s in the range of 40–50 μM. Cell Viability AssayCell Line: HEK 293T cell line Concentration: 100 μM Incubation Time: 16 hours Result: Specifically targeted MyD88 and dose-denpendently with TIR protein to reduced the inhibitory effect of MyD88-signaling. Western Blot AnalysisCell Line: HEK 293-I3A cells with MyD88 knockout Concentration: 1-500 μM Incubation Time: 13 hours Result: Dose-dependently inhibited TIR domain-mediated dimerization of full-length MyD88 and the recombinant TIR domain protein.In VivoT6167923 (0.17 and 1 mg; i.p. once) survives the mice from intoxication with SEB and LPS injection. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: 16-20 week-old BALB/c mice with LPS potentiation modelDosage: 0.17 and 1 mg Administration: Intraperitoneal injection; 0.17 and 1 mg once Result: Dose-dependently showed a therapeutic efficacy against SEB intoxication.Form:SolidIC50& Target:IC50: 2.7 μM (IFN-γ), 2.9 μM (IL-1β), 2.66 μM (IL-6), 2.66 μM (TNF-α). Specifications and Purity: 99%. Molecular Formula: C17H20BrN3O3S2. Molecular Weight: 458.39.