T6167923 B

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

T6167923 是一种选择性的 MyD88 依赖型信号通路的抑制剂。T6167923 直接与 MyD88 的 Toll/IL1 受体 (TIR) 结构域结合，破坏 MyD88 的同二聚体形成。T6167923 抑制 NF-κB 驱动的葡萄球菌肠毒素AP (SEAP) 活性，并且改善抗炎活性，对 IFN-γ，IL-1β，IL-6 和 TNF-α 的 IC50s 分别为 2.7 ?μM，2.9 μM，2.66 μM 和 2.66 μM。

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 IC50s of 2.7 ?μM, 2.9 μM, 2.66 μM and 2.66 μM for IFN-γ, IL-1β, IL-6 and TNF-α, respectively.

T6167923 (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 onMyD88-signaling.T6167923 (1-500 μM; 13 h) inhibits full-length MyD88 homodimeric formation.Cell Viability Assay Cell 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 IC50s of 2.66, 2.7, 2.66 and 2.9 μM in peripheral blood mono nuclear cells.Cell Viability Assay Cell 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 IC50s in the range of 40–50 μM.Cell Viability Assay Cell 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 Analysis Cell 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.

T6167923 (0.17 and 1 mg; i.p. once) survives the mice from intoxication with SEB and LPS injection.Animal Model:16-20 week-old BALB/c mice with LPS potentiation model Dosage:0.17 and 1 mg Administration: Intraperitoneal injection; 0.17 and 1 mg once Result:Dose-dependently showed a therapeutic efficacy against SEB intoxication.

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Immunology/Inflammation

MyD88

MyD88

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2437475-16-4

458.39

C17H20BrN3O3S2

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 250 mg/mL (545.39 mM; 超声助溶 ) H2O 中的溶解度 : < 0.1 mg/mL (insoluble)

C[C@H](NC(=O)N1CCN(CC1)S(=O)(=O)c1cccc(Br)c1)c1cccs1

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(-20℃)

With Ice Pack

≥ 2 years