Tofacitinib (CP-690550)

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

仅限科研使用

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。

Tofacitinib (CP-690550) Chemical Structure

CAS: 477600-75-2

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 3012.77 现货
大包装 有超大折扣

今日订购,明日送达 全国免运费 分装免费 分装成小规格产品(单支最小为1mg)
如1支10mg产品可分装为10支1mg产品

全国免费电话:400-668-6834   |   Email:info@selleck.cn

客户使用Selleck生产的Tofacitinib (CP-690550)发表文献136篇:

产品安全说明书

JAK抑制剂选择性比较

相关JAK产品

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 NUCy[|kxTnWwY4Tpc44hSXO|YYm= NHrkeGoxNjFxMD6zM|Eh|ryP MYiyOEBp NI\oS4FlcXO{dYD0d{DPu2NvY3jhbY4h[3m2b3vpcoUhe2mpbnHsbY5o MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN6M{K0NUc,OjF|OEOyOFE9N2F-
CD4+ T  NELrPFdHfW6ldHnvckBCe3OjeR?= NGjsRngyODBibl2= M2HrdVI1NzR6IHi= M1vNXYFjem:pYYTld{BETDNvaX7keYNm\CCyaH;zdIhwenmuYYTpc44hd2ZiU2TBWJM> MknoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF6OES1PFAoRjJzOEi0OVgxRC:jPh?=
CD4+ T  NVO5ZVRwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXKxNFAwPTByIH7N NX[5dnhtPDhiaB?= MonQbY5pcWKrdIOgZY51cS2FREOtbY5lfWOnZDDDSFQsyqCWIHPlcIwheHKxbHnm[ZJifGmxbh?= MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTh6NEW4NEc,OjF6OES1PFA9N2F-
CD4+ T  NXzVNmM1TnWwY4Tpc44hSXO|YYm= MV6yNE8yODBxNUCwJI5O NVTmZ2VOPDhiaB?= MmXTbY5pcWKrdIOgeIhmKGyndnXsd{Bw\iBiSVytOEwhUU[QLd8zMEBKVC1zN1GgZY5lKEmOLUKy M170TVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOEi0OVgxLz5{MUi4OFU5ODxxYU6=
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insect cells NYeyZmNOTnWwY4Tpc44h[XO|YYm= MlvxTY5pcWKrdHnvckBw\iCJU2SteIFo\2WmIFrhb|Ih\XiycnXzd4VlKGmwIHnud4VkfCClZXzsd{B2e2mwZzCyNEB2VSCDVGCsJGlEPTBiPTCwMlAyOiEQvF2u M1\RN|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUW1OlA2Lz5{MUG1OVYxPTxxYU6=
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PBMC M4fL[mZ2dmO2aX;uJIF{e2G7 M1vi[WlvcGmkaYTpc44hUUxvNz3pcoRkfWWmIGPURXQ2KHCqb4PwbI9zgWyjdHnvckBqdiCqdX3hckBRSk2FIHPlcIx{KGK7IH\sc5ch[3m2b33leJJ6NCCLQ{WwJF0hOC5yM{mg{txONg>? MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjl{N{SyN{c,OjZ7Mke0NlM9N2F-
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Huh7 NXzHNYJ7TnWwY4Tpc44h[XO|YYm= MXWxNEB2VQ>? MYizNEBucW6| NVnOO45oUW6qaXLpeIlwdiCxZjDUfYszKGmwIHj1cYFvKEi3aEegZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJI9nKGKjc3HsJIxmfmWuIGPURXQ{KHCqb4PwbI9zgWyjdHnvckBifCBzMDD1UUBi\nSncjCzNEBucW6|IHL5JIludXWwb3Lsc5R1cW6p MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjJ|MUG1PUc,OjZ{M{GxOVk9N2F-
Huh7 NHHqfGZHfW6ldHnvckBie3OjeR?= M1PmOlEhfU1? MkXEN|AhdWmwcx?= MUHJcohq[mm2aX;uJI9nKFS7a{KgbY4hcHWvYX6gTJVpPyClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25ib3[gTWZP[WyyaHG1MYlv\HWlZXSgV3RCXDNicHjvd5Bpd3K7bHH0bY9vKGG2IEGgeW0heHKnLXnuZ5Vj[XSnZDDmc5IhOzBibXnud{Bj\W[xcnWgTWZP[WyyaHG1JJN1cW23bHH0bY9vKG[xcjCzNEBucW6|IH3pcpMh[nliaX3teY5w[myxdITpcoc> M3f4fFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MkOxNVU6Lz5{NkKzNVE2QTxxYU6=
Assay
Methods Test Index PMID
Western blot JAK3 / STAT5 / p-STAT5 LMP1 / EBNA1 / BZLF1 JAK3 / p-JAK3 / STAT3 27732937 26082451
Growth inhibition assay Cell number 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]
  • 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]
  • 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。
动物实验:[1]
  • Animal Models: DBA/2 和 C57/BL6 小鼠
  • Dosages: 0-136 ng/mL
  • Administration: 渗透微泵输入

溶解度(25°C)

体外

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 3年 -20°C 粉状
2年 -80°C 溶于溶剂

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)

mg/kg g μL

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
%DMSO %

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,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法: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 ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意: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。

摩尔浓度计算器

质量 浓度 体积 分子量

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05082428 Active not recruiting -- Ulcerative Colitis Pfizer May 30 2022 --
NCT04768504 Recruiting Drug: Tofacitinib 10 mg Immune-Mediated Colitis Khashayar Esfahani|Sir Mortimer B. Davis - Jewish General Hospital March 22 2022 Phase 2
NCT05087589 Recruiting Drug: Tofacitinib Primary Sjögren''s Syndrome Peking University People''s Hospital November 20 2021 Phase 2
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
NCT04424303 Recruiting Drug: Tofacitinib Ulcerative Colitis Pfizer December 4 2020 --

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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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.