BMS-509744
(Synonyms: N-(5-((5-(4-乙酰基哌嗪-1-甲酰基)-4-甲氧基-2-甲基苯基)硫基)噻唑-2-基)-4-(((3,3-二甲基丁烷-2-基)氨基)甲基)苯甲酰胺,BMS 509744;BMS509744) 目录号 : GC10455
BMS-509744 是一种有效的、选择性的和 ATP 竞争性的 Itk 抑制剂，IC50 为 19 nM。
Cas No.:439575-02-7
Sample solution is provided at 25 µL, 10mM.
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BMS-509744 is a selective inhibitor of ITK with IC50 value of 15 nM [1].
ITK (IL-2-inducible T cell kinase) is an enzyme and plays an important role in T cell receptor signaling. It has been reported that ITK involves in the Th2-mediated inflammatory process and thus be regarded as a promising target for Th2-mediated inflammatory/immunosuppressive diseases treatment, such as asthma, rhinitis, allergies and atopic dermatitis [2].
BMS-509744 is a potent ITK inhibitor and is different from the reported ITK inhibitor RO5191614. When tested with human and murine cells, administration of BMS-509744 reduced TCR-induced functions by functioning on PLCgamma1 tyrosine phosphorylation, calcium mobilization, IL-2 secretion and T-cell proliferation [2]. In wild-typr HIV1 infected cells, BMS-509744 treatment blocked its infectivity and replication by inhibiting ITK, while has no effect on Nef-defective HIV1 infected cells [3].
In mouse model of ovalbuim-induced allergy/asthma, administration of BMS-509744 suppressed the production of IL-2 and significantly diminished lung inflammation by inhibiting ITK activity [2].
References:
[1].Kutach, A.K., et al., Crystal structures of IL-2-inducible T cell kinase complexed with inhibitors: insights into rational drug design and activity regulation. Chem Biol Drug Des, 2010. 76(2): p. 154-63.
[2].Lin, T.A., et al., Selective Itk inhibitors block T-cell activation and murine lung inflammation. Biochemistry, 2004. 43(34): p. 11056-62.
[3].Tarafdar, S., J.A. Poe, and T.E. Smithgall, The accessory factor Nef links HIV-1 to Tec/Btk kinases in an Src homology 3 domain-dependent manner. J Biol Chem, 2014. 289(22): p. 15718-28.
| Cell experiment [1]: | |
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Cell lines |
Jurkat T cells and A549 lung carcinoma cells |
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Preparation method |
This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0.1 ~ 10 μM |
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Applications |
In Jurkat T-cells, BMS-509744 dose-dependently inhibited tyrosine phosphorylation of phospholipase Cγ1 (PLCγ1) induced by anti-CD3 antibodies. In A549 lung carcinoma cells, Itk expression of which was not evident, BMS-509744 did not exhibit significant inhibition on cellular tyrosine or PLCγ1 phosphorylation induced by epidermal growth factors, at the concentration even up to 10 μM. |
| Animal experiment [1]: | |
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Animal models |
Mice |
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Dosage form |
5, 25 and 50 mg/kg; s.c. or i.p.; b.i.d., for 3 days |
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Applications |
In mice treated with anti-CD3 antibodies, BMS-509744 at the dose of 50 mg/kg inhibited IL-2 production by 50%. In a mouse model of ovalbumin-induced allergy/asthma, BMS-509744 dose-dependently reduced total cell and eosinophil infiltration into the lung, which indicated reduced lung inflammation. The reduction reached statistical significance at the dose of 25 mg/kg administered subcutaneously. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Lin, T.A., et al., Selective Itk inhibitors block T-cell activation and murine lung inflammation. Biochemistry, 2004. 43(34): p. 11056-62. | |
| Cas No. | 439575-02-7 | SDF | |
| 别名 | N-(5-((5-(4-乙酰基哌嗪-1-甲酰基)-4-甲氧基-2-甲基苯基)硫基)噻唑-2-基)-4-(((3,3-二甲基丁烷-2-基)氨基)甲基)苯甲酰胺,BMS 509744;BMS509744 | ||
| 化学名 | N-(5-((5-(4-acetylpiperazine-1-carbonyl)-4-methoxy-2-methylphenyl)thio)thiazol-2-yl)-4-(((3,3-dimethylbutan-2-yl)amino)methyl)benzamide | ||
| Canonical SMILES | CC1=C(SC(S2)=CN=C2NC(C3=CC=C(CNC(C(C)(C)C)C)C=C3)=O)C=C(C(N4CCN(C(C)=O)CC4)=O)C(OC)=C1 | ||
| 分子式 | C32H41N5O4S2 | 分子量 | 623.83 |
| 溶解度 | DMSO : 21.9 mg/mL (35.11 mM; Need ultrasonic and warming) | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.603 mL | 8.015 mL | 16.03 mL |
| 5 mM | 0.3206 mL | 1.603 mL | 3.206 mL |
| 10 mM | 0.1603 mL | 0.8015 mL | 1.603 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet