Takinib (EDHS-206) 是一种有效且选择性的TAK1抑制剂 (IC50=9.5 nM)，比 IRAK4 (IC50=120 nM) 和 IRAK1 (IC50=390 nM) 作用强 1.5 log 倍。Takinib 是一种TAK1自磷酸化的抑制剂，在 ATP 结合口袋内非竞争性结合。在类风湿关节炎和转移性乳腺癌细胞模型中，Takinib 诱导 TNF-α 刺激的细胞凋亡 (apoptosis)。Takinib 也是恶性疟原虫蛋白激酶 9 (PfPK9) 的抑制剂 (KD(app)of 0.46 nM)。
| 生物活性 | Takinib (EDHS-206) is an orally active and selectiveTAK1inhibitor (IC50=9.5 nM), more than 1.5 log more potent than the second and third ranked targets,IRAK4(120 nM) andIRAK1(390 nM), respectively. Takinib is an inhibitor of autophosphorylated TAK1 that non-competitively binds within the ATP binding pocket. Takinib inducesapoptosisfollowing TNFα stimulation in cell models of rheumatoid arthritis and metastatic breastcancer. Takinib is also aP. falciparumprotein kinase 9(PfPK9)inhibitor (KD(app)of 0.46 μM)[1][2][3]. |
| IC50& Target[1] | TAK1 9.5 nM (IC50) | IRAK4 120 nM (IC50) | IRAK1 390 nM (IC50) | GCK 430 nM (IC50) | CLK2 430 nM (IC50) | MINK1 1.9 μM (IC50) |
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体外研究
(In Vitro) | Takinib (10-10000 nM; 24 hours) induces apoptosis following TNF-α stimulation in MDA-MB-231 cells[1].
Takinib (10 μM; 0-1 hours) reduces phosphorylation of IKK and p65[1].
Takinib serves as a chemical starting point for the development ofPfPK9 (KD(app)of 0.46 μM) inhibitors for malaria[3].
Takinib (2 hours; 0.1-20 μM; human RASFs) induces phosphorylation of TAK1Thr184/187, STAT3Tyr705and STAT3Ser727in IL-1β-treated (10 ng/mL; 30 min) RASFs[4].
Western Blot Analysis[1] | Cell Line: | Breast cancer cell line MDA-MB-231 | | Concentration: | 10 μM | | Incubation Time: | 5, 15, 30, 60 minutes | | Result: | IKK and p65 were maximally phosphorylated at 15 minutes, which indicated activation of the NF-κB pathway, while p38 phosphorylation peaks at 30 minutes. |
Western Blot Analysis[4] | Cell Line: | IL-1β-treated (10 ng/mL; 30 min) RASFs | | Concentration: | 0.1-20 μM | | Incubation Time: | 2 hours | | Result: | Induced phosphorylation of TAK1Thr184/187, STAT3Tyr705and STAT3Ser727. |
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体内研究
(In Vivo) | Takinib (50 mg/kg; intraperitoneally; daily from days 18-36) reduces the clinical score in type II collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis[4].
Takinib (50 mg/kg; oral gavage; daily until 17 days) slows tumor growth in the Hodgkin lymphoma xenograft NSG mice[5].
| Animal Model: | Male DBA/1 mice (CIA arthritis model)[4] | | Dosage: | 50 mg/kg | | Administration: | Intraperitoneally; daily from days 18-36 | | Result: | Showed a reduction in clinical arthritic score compared to vehicle control. |
| Animal Model: | Female NSG mice (8 weeks old)[5] | | Dosage: | 50 mg/kg | | Administration: | Oral gavage; daily until 17 days | | Result: | Slowed tumor growth and reduced tumor size/weight. |
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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 : 50 mg/mL(155.11 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.1021 mL | 15.5106 mL | 31.0212 mL | | 5 mM | 0.6204 mL | 3.1021 mL | 6.2042 mL | | 10 mM | 0.3102 mL | 1.5511 mL | 3.1021 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: 2.5 mg/mL (7.76 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (7.76 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 25.0 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%corn oil Solubility: 2.5 mg/mL (7.76 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (7.76 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 25.0 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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