Tofacitinib (CP-690550)

For research use only. Not for use in humans.

Pfizer辉瑞授权 目录号:S2789 别名: Tasocitinib 中文名称:托法替尼,托法替布

Tofacitinib (CP-690550) Chemical Structure

CAS No. 477600-75-2

Tofacitinib (CP-690550,Tasocitinib)是一种新型JAK3抑制剂,在无细胞试验中IC50为1 nM,作用于JAK2和JAK1选择性低20到100倍。Tofacitinib 可在人类浆细胞样树突状细胞PDC中抑制抗凋亡的BCL-A1BCL-XL并诱导PDC凋亡。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 744.01 现货
RMB 582.19 现货
RMB 729.41 现货
RMB 2230.13 现货
RMB 3012.77 现货
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客户使用Selleck生产的Tofacitinib (CP-690550)发表文献124篇:

产品安全说明书

JAK抑制剂选择性比较

生物活性

产品描述 Tofacitinib (CP-690550,Tasocitinib)是一种新型JAK3抑制剂,在无细胞试验中IC50为1 nM,作用于JAK2和JAK1选择性低20到100倍。Tofacitinib 可在人类浆细胞样树突状细胞PDC中抑制抗凋亡的BCL-A1BCL-XL并诱导PDC凋亡。
靶点
JAK3 [1]
(Cell-free assay)
JAK2 [1]
(Cell-free assay)
JAK1 [1]
(Cell-free assay)
1 nM 20 nM 112 nM
体外研究

CP-690550 是特定的口服JAK3抑制剂, 作用于JAK2 和 JAK1,效果分别低20和100倍。CP-690550 对30种其他激酶没有作用效果,平均IC50 > 3000 nM。CP-690,550抑制IL-2诱导的增殖,比作用于GM-CSF诱导的增殖效果强30倍。[1] CP-690550 高效抑制小鼠混合淋巴反应(MLR)(IC50 = 91 nM)。[2] CP-690550 作用于小鼠 B细胞,有效抑制 IL-4 诱导的 CD23 (IC50=57 nM) 和II 类主要组织相容性复合体(MHCII) 表达上调,IC50=71 nM。[3]最新研究显示,通过加强 Th17分化,低剂量CP-690550加速实验性自身免疫脑脊髓炎的发生。[4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
T cells NUW4Umd{TnWwY4Tpc44hSXO|YYm= MWmwMlEwOC5|L{Gg{txO MXKyOEBp NFv4ToVlcXO{dYD0d{DPu2NvY3jhbY4h[3m2b3vpcoUhe2mpbnHsbY5o M1vBTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzM{izNlQyLz5{MUO4N|I1OTxxYU6=
CD4+ T  M2rOXWZ2dmO2aX;uJGF{e2G7 MYOxNFAhdk1? MlzVNlQwPDhiaB?= MYrhZpJw\2G2ZYOgR2Q{NWmwZIXj[YQheGixc4Doc5J6dGG2aX;uJI9nKFOWQWTz MmC0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF6OES1PFAoRjJzOEi0OVgxRC:jPh?=
CD4+ T  MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2rVelExOC93MECgcm0> M1XMZlQ5KGh? NX;ROllscW6qaXLpeJMh[W62aT3DSFMucW6mdXPl[EBETDRtwrDUJINmdGxicILvcIln\XKjdHnvci=> M{nUV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOEi0OVgxLz5{MUi4OFU5ODxxYU6=
CD4+ T  NUTqT4p[TnWwY4Tpc44hSXO|YYm= M3rjfVIxNzFyMD:1NFAhdk1? MlHPOFghcA>? M4LxdolvcGmkaYTzJJRp\SCuZY\lcJMhd2ZiIFnMMVQtKEmITj5Ot{whUUxvMUfBJIFv\CCLTD2yNi=> M{TXSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOEi0OVgxLz5{MUi4OFU5ODxxYU6=
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Sf9 M{jRV2Z2dmO2aX;uJIF{e2G7 NGrNWYI6OCCvaX7z M{ntb2lvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRiTj30[ZJucW6jbDDHV3QufGGpZ3XkJGpCUzNiZYjwdoV{e2WmIHnuJHNnQSClZXzsd{B2e2mwZzDCbY91cW5vTFOtSXFGTEWSRVfEXWZGX0yHIHHzJJN2[nO2cnH0[UBi\nSncjC5NEBucW6|IHL5JHRTNU[URWSgZZN{[XluIFnDOVAhRSByLkCwNFYh|ryPLh?= NY\PT2dpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwPFc4PTBpPkKyNFg4PzVyPD;hQi=>
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insect cells NWTrWXI5TnWwY4Tpc44h[XO|YYm= NIm1c29KdmirYnn0bY9vKG:oIFfTWE11[WepZXSgToFsOSCneIDy[ZN{\WRiaX6gbY5{\WO2IHPlcIx{KHW|aX7nJFcxKHWPIFHUVEwhUUN3MDC9JFAvODB4MTFOwG0v NVq4[403RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxOVU3ODVpPkKxNVU2PjB3PD;hQi=>
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insect cells NVjlPJFWTnWwY4Tpc44h[XO|YYm= M3LzNWlvcGmkaYTpc44hd2ZiR2PUMZRi\2enZDDKZYszKGW6cILld5Nm\CCrbjDpcpNm[3RiY3XscJMhfXOrbnegNlAhfU1iQWTQMEBKSzVyIE2gNE4xOTJizszNMi=> NIe4Omw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUG1OVYxPSd-MkGxOVU3ODV:L3G+
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Huh7 NHjNe3RHfW6ldHnvckBie3OjeR?= MlTtNUB2VQ>? NVj4bYk5OzBibXnudy=> NHnPOIZKdmirYnn0bY9vKG:oIGT5b|IhcW5iaIXtZY4hUHWqNzDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gc4YhUU[QYXzwbIE2NWmwZIXj[YQhW1SDVEOgdIhwe3Cqb4L5cIF1cW:wIHH0JFEhfU1icILlMYlv[3WkYYTl[EBnd3JiM{CgcYlveyCkZX\vdoUhUU[QYXzwbIE2KHO2aX31cIF1cW:wIH\vdkA{OCCvaX7zJI1qdnNiYomgbY1ufW6xYnzveJRqdmd? MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjJ|MUG1PUc,OjZ{M{GxOVk9N2F-

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
JAK3 / STAT5 / p-STAT5 ; 

PubMed: 27732937     


The following cell lines: EBV-negative B cell line (BJAB), EBV-transformed lymphoblastoid cell line (LCL), EBV-negative T cell lines (Jurkat and MOLT4), EBV-positive T cell lines (SNT15 and SNT16), EBV-negative NK cell line (KHYG1), and EBV-positive NK cell lines (KAI3 and SNK6), were treated without (−) or with (+) 1 μM tofacitinib for 24 h and cell lysates were then immunoblotted for the indicated proteins.

LMP1 / EBNA1 / BZLF1 ; 

PubMed: 27732937     


SNT13, SNT15, SNT16, KAI3 and SNK6 cell lines were treated with 5 μM tofacitinib for 48 h, and cell lysates were immunoblotted for LMP1, EBNA1 and BZLF1. Actin was blotted as a loading control.

JAK3 / p-JAK3 / STAT3 ; 

PubMed: 26082451     


CTCL cell lines were subjected to western blot (tofacitinib 10, 100, 200 nM) (G) after 48 hours of treatment.

27732937 26082451
Growth inhibition assay
Cell number ; 

PubMed: 27732937     


BJAB, LCL, Jurkat, SNT15, KHYG1 and KAI3 cells were treated with the indicated concentrations of tofacitinib, and viable cells were counted at the indicated times using the trypan blue exclusion test. Values are means ± SE of the results from triplicate experiments. *P < 0.05 as compared with DMSO-treated cells.

27732937
体内研究 CP-690550作用于异位心脏移植(DBA2供体心脏移到C57/BL6宿主 )的小鼠模型,提高移植后心脏的寿命,这种作用存在剂量依赖性。EC50(50%小鼠将保持移植 >28天时血液中药物浓度) 为~60 ng/mL。CP-690550 作用于非人灵长类动物 (NHPs, 食蟹猴) (50 到100 ng/ml剂量实验组和200 到400 ng/ml剂量实验组的MST分别为62和83天),防止同种异体肾移植的排斥反应。[1] CP-690550 每天按1.5-15 mg/kg剂量长期作用于小鼠,通过流式细胞仪检测,发现淋巴细胞亚群发生改变,这种作用存在剂量和时间依赖性。处理21天,观察到最显著的变化是脾NK1.1+TCRb 细胞数降低96%。CP-690550 按1.87-30 mg/kg剂量皮下注射给药敏感小鼠,延迟型过敏反应降低,这种作用存在剂量依赖性。

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[1]
- 合并

JAK3 激酶实验:

全长cDNA中编码人JAK3 催化结构域(785aa到 1125aa, JH1 催化结构域)的片段通过PCR放大,且克隆到杆状病毒转移载体 pVL1393的EcoRI位点。使用重组杆状病毒感染 Sf9 细胞,在谷胱甘肽琼脂糖凝胶上分离重组 GSTJAK3融合蛋白。使用还原型谷胱甘肽洗脱融合蛋白,然后储存在含50 mM Tris, pH 7.5, 10 mM DTT 和 10% 甘油的缓冲液中。通过ELISA按如下测量JAK3激酶活性: 使用随机L-谷氨酸和酪氨酸共聚物 (4:1) (100 ug/mL)包被实验板过夜。冲洗实验板,在有或无抑制剂时,重组JAK3 JH1:GST(每孔100 ng)在室温下温育30分钟,然后加入HRP结合的PY20抗磷酸酪氨酸抗体(ICN),然后通过TMB(3,3’,5,5’-四甲基联苯胺)电泳。使用 ELISA法测定酪氨酸激酶催化活性,而通过放射性酶实验测定丝/苏氨酸激酶。
细胞实验:[1]
- 合并
  • Cell lines: 人类T 细胞
  • Concentrations: 0-4000 nM
  • Incubation Time: 4天
  • Method: 为了测量 IL-2依赖的增殖,分离的淋巴细胞按1-2 × 106/mL密度再悬浮在完全RPMI培养基(RPMI 1640含 10% (w/v)胎牛血清(FCS), 1%(w/v) 青霉素和链霉素 )中。加入植物血细胞凝集素(PHA),终浓度为10mg/mL, 培养物在37oC 下含 5% (v/v) CO2 湿润孵育器中温育3天,用于上调IL-2R 和 JAK3 表达。在有或无CP-690,550 时,加入 IL-2 (200U/mL), 细胞在 37oC下含 5% (v/v) CO2湿润孵育器中温育,72小时后加入50 mL 3H-胸甘(5mCi/mL)。实验板再温育18小时,使用 96孔收集器收集,然后在闪烁计数器中计数。HUO3细胞培养在含粒细胞-巨噬细胞集落刺激因子的培养基中,人包皮成纤维细胞培养在含10% 胎牛血清的培养基中。在新鲜培养的细胞中加入CP-690550,培养4天。在培养期的最后18小时,加入3 H胸甘。
    (Only for Reference)
动物实验:[1]
- 合并
  • Animal Models: DBA/2 和 C57/BL6 小鼠
  • Dosages: 0-136 ng/mL
  • Administration: 渗透微泵输入
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 62 mg/mL warmed (198.48 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
2% DMSO+30% PEG 300+ddH2O
5mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 312.37
化学式

C16H20N6O

CAS号 477600-75-2
储存条件 粉状
溶于溶剂
别名 Tasocitinib

动物体内配方计算器 (澄清溶液)

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
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Selleck为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % ddH2O
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04624230 Recruiting Drug: tofacitinib Ulcerative Colitis Pfizer August 12 2021 Phase 3
NCT04496960 Recruiting Drug: tofacitinib|Other: Placebo Sjogren''s Syndrome National Institute of Dental and Craniofacial Research (NIDCR)|National Institutes of Health Clinical Center (CC) May 18 2021 Phase 1|Phase 2
NCT04768504 Not yet recruiting Drug: Tofacitinib 10 mg Immune-Mediated Colitis Khashayar Esfahani|Sir Mortimer B. Davis - Jewish General Hospital April 2021 Phase 2
NCT04424303 Recruiting Drug: Tofacitinib Ulcerative Colitis Pfizer December 7 2020 --
NCT04468425 Recruiting Drug: Tofacitinib Citrate Healthy Subjects TWi Biotechnology Inc. October 14 2020 Phase 1
NCT04338204 Recruiting Drug: tofacitinib Ulcerative Colitis Pfizer September 14 2020 --

技术支持

在订购、运输、储存和使用我们的产品的任何阶段,您遇到的任何问题,均可以通过拨打我们的热线电话400-668-6834,或者技术支持邮箱tech@selleck.cn,直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题,请给我们留言。

  • * 必填项

常见问题及建议解决方法

  • 问题 1:

    I was just wondering what the main differences between S2789 and S5001?

  • 回答:

    S2789(Tofacitinib (CP-690550)) is the base form of S5001 (Tofacitinib (CP-690550) Citrate). The biological activity of these two compounds are same. The S5001 (Tofacitinib (CP-690550) Citrate) is more suitable for oral administration.

JAK Signaling Pathway Map

JAK Inhibitors with Unique Features

相关JAK产品

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID