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。
| 生物活性 | T6167923 is a selective inhibitor ofMyD88-dependent signalingpathways. T6167923 directly binds to Toll/IL1 receptor (TIR) domain ofMyD88and disruptsMyD88homodimeric formation. T6167923 inhibitsNF-κBdriven Staphylococcus enterotoxin AP (SEAP) activity, and improves anti-inflammatory activity withIC50s of 2.7 μM, 2.9 μM, 2.66 μM and 2.66 μM forIFN-γ, IL-1β,IL-6and TNF-α, respectively[1][2]. |
| IC50& Target | IC50: 2.7 μM (IFN-γ), 2.9 μM (IL-1β), 2.66 μM (IL-6), 2.66 μM (TNF-α)[2] |
体外研究
(In Vitro) | T6167923 (0-500 μM; 20 h) inhibits the pro-inflammatory cytokine response of staphylococcal enterotoxin B (SEB) in peripheral blood mono nuclear cells[2].T6167923 (10-500 μM; 2 h) inhibits secreted alkaline phosphatase response (SEAP) expression in HEK 293T cells[2].T6167923 (100 μM; 16 h) binds to TIR protein and reduced the inhibitory effect on MyD88-signaling[2].T6167923 (1-500 μM; 13 h) inhibits full-length MyD88 homodimeric formation[2].
Cell Viability Assay[2] | 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[2] | 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[2] | 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[2] | 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. |
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体内研究
(In Vivo) | T6167923 (0.17 and 1 mg; i.p. once) survives the mice from intoxication with SEB and LPS injection[2].
| Animal Model: | 16-20 week-old BALB/c mice with LPS potentiation model[2] | | 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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 250 mg/mL(545.39 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.1815 mL | 10.9077 mL | 21.8155 mL | | 5 mM | 0.4363 mL | 2.1815 mL | 4.3631 mL | | 10 mM | 0.2182 mL | 1.0908 mL | 2.1815 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (4.54 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.54 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (4.54 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.54 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (4.54 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.54 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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