Tofacitinib (CP-690550) Citrate

Pfizer辉瑞授权 目录号:S5001 别名: Tasocitinib Citrate 中文名称:托法替尼

仅限科研使用

Tofacitinib citrate (CP-690550, Tasocitinib)是一种新型JAK抑制剂,对JAK3,JAK2,JAK1的IC50分别为1 nM, 20 nM 和112 nM。Tofacitinib citrate 还具有抗感染的活性。

Tofacitinib (CP-690550) Citrate Chemical Structure

CAS: 540737-29-9

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 1561.36 现货
RMB 1194.19 现货
RMB 3843.17 现货
大包装 有超大折扣
大剂量询单有大折扣!

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如1支10mg产品可分装为10支1mg产品

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客户使用Selleck生产的Tofacitinib (CP-690550) Citrate发表文献177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 citrate (CP-690550, Tasocitinib)是一种新型JAK抑制剂,对JAK3,JAK2,JAK1的IC50分别为1 nM, 20 nM 和112 nM。Tofacitinib citrate 还具有抗感染的活性。
靶点
JAK3 [1]
(Cell-free assay)
JAK2 [4]
(Cell-free assay)
1 nM 20 nM
体外研究

CP-690550抑制IL-2调节的人T细胞爆发式增殖,和IL-15诱导的CD69表达,IC50分别为11和48 nM。CP-690550抑制混合淋巴细胞反应,IC50为87 nM。CPCP-690550 处理含人野生型或V617F JAK2的鼠因子依赖的细胞Patersen–促红细胞生成素受体(FDCP-EpoR) 细胞,抑制细胞增殖,IC50分别为2.1 µM 和0.25 µM。CP-690550 抑制白细胞介素-6诱导的STAT1 和STAT3磷酸化,IC50分别为23和77 nM。而且, CP-690550作用于携带JAK2V617F的小鼠 FDCP-EpoR细胞,具有显著的促凋亡作用,然而效果比作用于携带野生型JAK2的细胞低。伴随着抑制关键JAK2V617F依赖的下游信号效应器信号转导的磷酸化,及(STAT)3, STAT5, 和v-akt小鼠胸腺瘤病毒癌基因同源(AKT)的转录激活。[2] 此外, CP-690550 在体外作用于人猕猴 NK 和CD8+ T 细胞,抑制IL-15诱导的CD69表达。[3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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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 作用于小鼠模型,降低迟发型超敏感反应和延长心脏移植存活。而且, CP-690550 处理来自JAK2V617F阳性 PV患者体内外膨胀的红系祖细胞,产生特定的抗增殖(IC50 = 0.2 µM) 和促凋亡活性。 相反, 在增殖(IC50 > 1.0 µM)和凋亡检测时,从健康对照组中的膨胀祖细胞对CP-690550敏感性低很多。 [2] CP-690550按 10和30 mg/kg剂量每天处理NK细胞,持续处理2周,与对照组相比,细胞数显著降低,这种作用存在时间依赖性。 CP-690550处理实验组的动物效应小样记忆CD8+ 细胞数比对照组低55% 。[3]

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]

  • 酶实验:

    进行JAK1, JAK2, 和JAK3 激酶实验,使用在杆状病毒感染的 SF9细胞中表达的蛋白(GST 和人类JAK酶催化结构域的融合蛋白),通过亲和层析在谷胱甘肽-琼脂糖凝胶中纯化。反应底物是聚谷氨酸-酪氨酸 [PGT (4:1)], 按100 μg/mL包被到Nunc Maxi Sorp板上,在 37oC下过夜。然后冲洗板三次, 在每孔中加入JAK 酶,孔中含100 μL激酶buffer(50 mM HEPES, pH 7.3, 125 mM NaCl, 24 mM MgCl2) + ATP + 1 mM 钒酸钠)。按不同剂量加入CP-690550,进行激酶实验。然后在室温下温育30分钟,再冲洗实验板三次。通过标准ELISA实验,使用 磷酸化抗体测定一个给定孔中的磷酸化的酪氨酸水平。

细胞实验:

[2]

  • Cell lines: HEL细胞, 扩增的红系祖细胞
  • Concentrations: 0.1 μM,1 μM
  • Incubation Time: 40分钟
  • Method:

    HEL细胞, 从正常供着,两个PV病人体内获得的扩大红系祖细胞,和 FDCP-EpoR受体细胞(每组样本2 × 107 个细胞),使用浓度不断增高的 CP-690550处理, 然后在不同时间点收集。细胞制成颗粒,使用冷磷酸盐缓冲液冲洗三次,然后悬浮在300 µL裂解液中 ,再在冰上处理1小时。细胞裂解液按20 000g转速在 4oC下离心20分钟,取出上清液。在上清液中加入15 µL anti-JAK2 (处理细胞) 或 anti-JAK3 兔抗体(未处理细胞),然后在冰上再处理1小时。最后, 在上清液中加入50 µL 蛋白A/G琼脂糖浆,然后在 4oC下不断旋转温育过夜。冲洗抗体-蛋白复合体三次, 再使用放射免疫沉淀法(RIPA) buffer冲洗一次,使用冲洗冲洗一次,最后使用50 mM Tris-HCl buffer pH 为7.5冲洗一次。通过 Western blotting 分析免疫沉淀复合物,使用磷酸酪氨酸抗体,除去,再使用anti-JAK2和anti-JAK3抗体做探针,来分析免疫沉淀复合物。

动物实验:

[2]

  • Animal Models: 毛里求斯成年猕猴
  • Dosages: 10, 30 mg/kg/d
  • Administration: 口服饲喂

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):
0.5% methylcellulose

30 mg/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 504.49
化学式

C16H20N6O.C6H8O7

CAS号 540737-29-9
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 Not yet recruiting -- Ulcerative Colitis Pfizer December 1 2021 --
NCT05087589 Recruiting Drug: Tofacitinib Primary Sjögren''s Syndrome Peking University People''s Hospital November 18 2021 Phase 2
NCT04768504 Recruiting Drug: Tofacitinib 10 mg Immune-Mediated Colitis Khashayar Esfahani|Sir Mortimer B. Davis - Jewish General Hospital November 15 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 7 2020 --

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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常见问题及建议解决方法

问题 1:
What is the difference between the two products (S5001, S2789)?

回答:
Tofacitinib (S2789) is the base form of Tofacitinib citrate (S5001). The biological activity of these two compound are same. S5001 is better than S2789 for Oral gavage.