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Tofacitinib citrate

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Chemical Structure| 540737-29-9 同义名 : 柠檬酸托法替尼 ;Tasocitinib citrate;CP-690550 citrate;CP 690,550;Tofacitinib (citrate)
CAS号 : 540737-29-9
货号 : A118834
分子式 : C22H28N6O8
纯度 : 99%
分子量 : 504.493
MDL号 : MFCD11616529
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(49.55 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

H2O: 3 mg/mL(5.95 mM)，配合低频超声助溶
动物实验配方：

IP 2% DMSO+water 2 mg/mL clear

PO 0.5% CMC-Na 80 mg/mL suspension

生物活性
靶点

  • 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[3]. 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[1].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
Ba/F3 cells Function assay 60 mins Inhibition of TEL-fused JAK1 expressed in Ba/F3 cells assessed as inhibition of STAT5 phosphorylation after 60 mins by AlphaScreen assay, IC50=26 nM. 22087750
Ba/F3 cells Function assay 60 mins Inhibition of TEL-fused JAK3 expressed in Ba/F3 cells assessed as inhibition of STAT5 phosphorylation after 60 mins by AlphaScreen assay, IC50=54 nM. 22087750
human CD4+ T cells 5 to 500 nM Function assay 1 h Inhibition of IL2-induced Stat5 phosphorylation in human CD4+ T cells at 5 to 500 nM after 1 hr by Western blot 19053756
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01023100 Arthritis, Rheumatoid Phase 1 Completed - United States, Massachusetts ... 展开 >> Pfizer Investigational Site Woburn, Massachusetts, United States, 01801 收起 <<
NCT01185184 Healthy Phase 1 Completed - Singapore ... 展开 >> Pfizer Investigational Site Singapore, Singapore, 188770 收起 <<
NCT01246583 Psoriasis Phase 2 Completed - United States, Alabama ... 展开 >> Pfizer Investigational Site Mobile, Alabama, United States, 36606 United States, California Pfizer Investigational Site Los Angeles, California, United States, 90045 United States, Florida Pfizer Investigational Site Orange Park, Florida, United States, 32073 United States, Nebraska Pfizer Investigational Site Omaha, Nebraska, United States, 68144 United States, New Mexico Pfizer Investigational Site Albuquerque, New Mexico, United States, 87106 United States, South Dakota Pfizer Investigational Site Rapid City, South Dakota, United States, 57702 United States, Texas Pfizer Investigational Site Dallas, Texas, United States, 75231 Canada, Ontario Pfizer Investigational Site Waterloo, Ontario, Canada, N2J 1C4 Canada, Quebec Pfizer Investigational Site Montreal, Quebec, Canada, H2K 4L5 Pfizer Investigational Site Montreal, Quebec, Canada, H3Z 2S6 Canada Pfizer Investigational Site Quebec, Canada, G1V 4X7 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.98mL

0.40mL

0.20mL

9.91mL

1.98mL

0.99mL

19.82mL

3.96mL

1.98mL
参考文献

[1]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.

[2]Lloyd-Lavery A. Long-term safety data for tofacitinib, an oral Janus kinase inhibitor, for the treatment for psoriasis. Br J Dermatol. 2018;179(4):815-816.

[3]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.