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Tofacitinib

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Chemical Structure| 477600-75-2 同义名 : Tasocitinib;CP-690550
CAS号 : 477600-75-2
货号 : A280750
分子式 : C16H20N6O
纯度 : 98%
分子量 : 312.37
MDL号 : MFCD11035919
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(384.16 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 2.5 mg/mL(8 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

IP 2% DMSO+water 2 mg/mL clear

PO 0.5% CMC-Na 61 mg/mL suspension

生物活性
靶点

  • JAK1

    JAK1, IC50:112 nM

  • JAK3

    JAK3, IC50:1 nM

  • JAK2

    JAK2, IC50:20 nM
描述 Tofacitinib Citrate is the citrate form of Tofacitinib. Tofacitinib is an ATP-competed inhibitor of JAK with IC50 values of 3.2±1.4 nM, 4.1±0.4 nM, 1.6±0.2 nM, 34.0±6.0 nM for JAK1, JAK2, JAK3 and TYK2 in in vitro enzyme assays. It competes with ATP for binding to the active site of the kinase domain of JAKs with Ki values of 0.68 ± 0.12 nM (JAK1), 0.99 ± 0.04 nM (JAK2), 0.24 ± 0.02 nM (JAK3) and 4.39 ± 0.27 nM (TYK2). Tofacitinib potently inhibits multiple cytokine activated JAK/STAT signaling pathways in normal human, mouse or rat whole blood with IC50s below 200 nM. Selectivity assessed in mouse and rat whole blood shows that tofacitinib appears to be more potently to JAK1 and JAK3. In cell assays, tofacitinib inhibits human total myeloid and CFU-G colony formation with IC50s of 0.87 and 0.93 μM. In AIA rats, tofacitinib treatment can decrease paw volume and disease-elevated neutrophil count to normal range compared to vehicle treated control rats. Tofacitinib treatment also dose-dependently decreased both IL-17 and IL-6 of the AIA-induced increase compared to control levels with an approximately 80% inhibition. It significantly inhibits the AIA-induced increase in maturing myeloid cells by approximately 50% at the 10 mg/kg dose[6]. Tofacitinib has been approved by the U.S. Food and Drug Administration and European Medicines Agency for the treatment of rheumatoid arthritis (RA), psoriatic arthritis and ulcerative colitis[2].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
CD4+ T 20/100/500 nM Function Assay 48 h inhibits the levels of IL-4, IFN-γ, IL-17A and IL-22 21884580
CD4+ T 100/500 nM Growth Inhibition Assay 48 h inhibits anti-CD3-induced CD4+ T cell proliferation 21884580
CD4+ T 100 nM Function Assay 24/48 h abrogates CD3-induced phosphorylation of STATs 21884580
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.20mL

0.64mL

0.32mL

16.01mL

3.20mL

1.60mL

32.01mL

6.40mL

3.20mL
参考文献

[1]Meyer DM, Jesson MI, et al. Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis. J Inflamm (Lond). 2010 Aug 11;7:41.

[2]Meyer DM, Jesson MI, Li X, Elrick MM, Funckes-Shippy CL, Warner JD, Gross CJ, Dowty ME, Ramaiah SK, Hirsch JL, Saabye MJ, Barks JL, Kishore N, Morris DL. Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis. J Inflamm (Lond). 2010 Aug 11;7:41. doi: 10.1186/1476-9255-7-41. PMID: 20701804; PMCID: PMC2928212.

[3]Lee JS, Kim SH, et al. Dose-Dependent Pharmacokinetics of Tofacitinib in Rats: Influence of Hepatic and Intestinal First-Pass Metabolism. Pharmaceutics. 2019 Jul 5;11(7). pii: E318.

[4]Tofacitinib

[5]Xeljanz

[6]Lloyd-Lavery A. Long-term safety data for tofacitinib, an oral Janus kinase inhibitor, for the treatment for psoriasis. Br J Dermatol. 2018 Oct;179(4):815-816. doi: 10.1111/bjd.17016. PMID: 30318813.