Takinib(Synonyms: EDHS-206)

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Takinib (Synonyms: EDHS-206) 纯度: 99.15%

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)。

Takinib(Synonyms: EDHS-206)

Takinib Chemical Structure

CAS No. : 1111556-37-6

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10 mM * 1 mL in DMSO ￥851 In-stock
5 mg ￥1200 In-stock
10 mg ￥1500 In-stock
50 mg ￥6000 In-stock
100 mg ￥11000 In-stock
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Takinib 相关产品

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生物活性

Takinib (EDHS-206) is an orally active and selective TAK1 inhibitor (IC50=9.5 nM), more than 1.5 log more potent than the second and third ranked targets, IRAK4 (120 nM) and IRAK1 (390 nM), respectively. Takinib is an inhibitor of autophosphorylated TAK1 that non-competitively binds within the ATP binding pocket. Takinib induces apoptosis following TNFα stimulation in cell models of rheumatoid arthritis and metastatic breast cancer. Takinib is also a P. falciparum protein 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)

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 of PfPK9 (KD(app) of 0.46 μM) inhibitors for malaria[3].
Takinib (2 hours; 0.1-20 µM; human RASFs) induces phosphorylation of TAK1Thr184/187, STAT3Tyr705 and STAT3Ser727 in IL-1β-treated (10 ng/mL; 30 min) RASFs[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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, STAT3Tyr705 and STAT3Ser727.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

分子量

322.36

Formula

C18H18N4O2
CAS 号

1111556-37-6
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
溶解性数据
In Vitro: 

DMSO : 50 mg/mL (155.11 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 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。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

  • 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 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Totzke J, et al. Takinib, a Selective TAK1 Inhibitor, Broadens the Therapeutic Efficacy of TNF-α Inhibition for Cancer and Autoimmune Disease. Cell Chem Biol. 2017 Aug 17;24(8):1029-1039.

    [2]. Scarneo SA, et.al. Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice. Arthritis Res Ther. 2019 Dec 17;21(1):292.

    [3]. Raphemot R, et al. Plasmodium PK9 Inhibitors Promote Growth of Liver-Stage Parasites. Cell Chem Biol. 2019 Mar 21;26(3):411-419.e7.

    [4]. Panipinto PM, et.al. Takinib Inhibits Inflammation in Human Rheumatoid Arthritis Synovial Fibroblasts by Targeting the Janus Kinase-Signal Transducer and Activator of Transcription 3 (JAK/STAT3) Pathway. Int J Mol Sci. 2021;22(22):12580. Published 2021 Nov 22.

    [5]. Song Z,et.al. Essential role of the linear ubiquitin chain assembly complex and TAK1 kinase in A20 mutant Hodgkin lymphoma. Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28980-28991.

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