货号:A118834
同义名:
柠檬酸托法替尼
/ Tasocitinib citrate; CP-690550 citrate
Tofacitinib citrate是一种口服有效的JAK1/2/3抑制剂,其IC50值分别为1、20和112 nM。它还具有抗细菌、抗真菌和抗病毒特性。


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| 产品名称 | JAK1 ↓ ↑ | JAK2 ↓ ↑ | JAK3 ↓ ↑ | Tyk2 ↓ ↑ | 其他靶点 | 纯度 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Decernotinib |
+++
JAK1, IC50: 11 nM JAK1, Ki: 11 nM |
+++
JAK2, Ki: 13 nM |
++++
JAK3, Ki: 2.5 nM |
+++
TYK2, Ki: 13 nM |
99%+ | ||||||||||||||
| ZM39923 HCl |
+
JAK1, pIC50: 4.4 |
+
JAK3, pIC50: 7.1 |
EGFR | 97% | |||||||||||||||
| Cerdulatinib |
+++
JAK1, IC50: 12 nM |
+++
JAK2, IC50: 6 nM |
+++
JAK3, IC50: 8 nM |
++++
TYK2, IC50: 0.5 nM |
99%+ | ||||||||||||||
| Momelotinib |
+++
JAK1, IC50: 11 nM |
++
JAK2, IC50: 18 nM |
+
JAK3, IC50: 155 nM |
99%+ | |||||||||||||||
| XL019 |
+
JAK1, IC50: 134.3 nM |
++++
JAK2, IC50: 2.2 nM |
+
JAK3, IC50: 214.2 nM |
FLT3 | 99%+ | ||||||||||||||
| Ruxolitinib |
+++
JAK1, IC50: 3.3 nM |
++++
JAK2, IC50: 2.8 nM |
98% | ||||||||||||||||
| Tofacitinib |
+
JAK1, IC50: 112 nM |
++
JAK2, IC50: 20 nM |
++++
JAK3, IC50: 1 nM |
98% | |||||||||||||||
| Ruxolitinib (S enantiomer) |
+++
JAK1, IC50: 3.3 nM |
++++
JAK2, IC50: 2.8 nM |
++
TYK2, IC50: 19 nM |
98% | |||||||||||||||
| Filgotinib |
+++
JAK1, IC50: 10 nM |
++
JAK2, IC50: 28 nM |
+
JAK3, IC50: 810 nM |
+
TYK2, IC50: 116 nM |
99% | ||||||||||||||
| Baricitinib |
+++
JAK1, IC50: 5.9 nM |
+++
JAK2, IC50: 5.7 nM |
++
TYK2, IC50: 53 nM |
99% | |||||||||||||||
| Gandotinib |
++
JAK1, IC50: 19.8 nM |
++++
JAK2 (V617F), Ki: 0.245 nM JAK2, IC50: 0.288 nM |
++
JAK3, IC50: 48.0 nM |
++
TYK2, IC50: 44 nM |
FLT3 | 99%+ | |||||||||||||
| Oclacitinib maleate |
+++
JAK1, IC50: 10nM |
++
JAK2, IC50: 18nM |
+
JAK3, IC50: 99nM |
+
TYK2, IC50: 84nM |
98+% | ||||||||||||||
| NVP-BSK805 2HCl |
++
JAK1, IC50: 31.63 nM |
++++
JAK2, IC50: ~0.5 nM |
++
JAK3, IC50: 18.68 nM |
+++
TYK2, IC50: 10.76 nM |
95% | ||||||||||||||
| Peficitinib | ✔ | 98% | |||||||||||||||||
| Go6976 | ✔ | FLT3 | 99%+ | ||||||||||||||||
| AZD-1480 |
++++
JAK2, IC50: 0.26 nM |
99%+ | |||||||||||||||||
| Fedratinib |
+++
JAK2, IC50: 3 nM JAK2 (V617F), IC50: 3 nM |
RET,FLT3 | 99%+ | ||||||||||||||||
| WP1066 |
+
JAK2, IC50: 2.3 μM |
98% | |||||||||||||||||
| Curcumol | ✔ | 98% | |||||||||||||||||
| AZ960 |
++++
JAK2, Ki: 0.45 nM JAK2, IC50: <3 nM |
97% | |||||||||||||||||
| GLPG0634 analog | ✔ | 99%+ | |||||||||||||||||
| CEP-33779 |
++++
JAK2, IC50: 1.8 nM |
99%+ | |||||||||||||||||
| FLLL32 |
+
JAK2, IC50: <5 μM |
99%+ | |||||||||||||||||
| WHI-P154 |
+
JAK3, IC50: 1.8 μM |
VEGFR,Src,EGFR | 98% | ||||||||||||||||
| BMS-911543 |
++++
JAK2, IC50: 1.1 nM |
+
JAK3, IC50: 75 nM |
++
TYK2, IC50: 66 nM |
95% | |||||||||||||||
| TG101209 |
+++
JAK2, IC50: 6 nM |
+
JAK3, IC50: 169 nM |
RET,FLT3 | 99%+ | |||||||||||||||
| AT9283 |
++++
JAK2, IC50: 1.2 nM |
++++
JAK3, IC50: 1.1 nM |
99%+ | ||||||||||||||||
| Pacritinib |
++
JAK2, IC50: 23 nM JAK2 (V617F), IC50: 19 nM |
+
JAK3, IC50: 520 nM |
++
TYK2, IC50: 50 nM |
FLT3 | 97% | ||||||||||||||
| Tofacitinib citrate |
++
JAK2, IC50: 20 nM |
++++
JAK3, IC50: 1 nM |
99% | ||||||||||||||||
| FM-381 |
++++
JAK3, IC50: 127 pM |
98% | |||||||||||||||||
| 1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。 | |||||||||||||||||||
| 靶点 |
|
| 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]. |
| Concentration | Treated Time | Description | References | |
| CTL effectors from C3H/HeJ mice | 50 nM | 96 h | Tofacitinib blocked IL-15–triggered pSTAT5 activation | Nat Med. 2014 Sep;20(9):1043-9. |
| human rheumatoid arthritis synovial fibroblasts (RASFs) | 5 µM | 2 h | Inhibition of IL-6/IL-6R-induced JAK/STAT signaling and p-Akt activation | Front Immunol. 2021 Nov 2;12:746503. |
| Bone marrow-derived macrophages (BMDM) | 300 nM | 24, 48, 96 h | To evaluate the effect of Tofacitinib on TNF-α and IL-1β levels in M.tb-infected BMDM cells. Results showed that Tofacitinib treatment did not significantly alter cytokine levels. | EBioMedicine. 2015 Jul 14;2(8):868-73. |
| NK-S1 cells | 1.0 μM | 72 h | To detect the effect of Tofacitinib on cell cycle and apoptosis, the results showed that Tofacitinib induced G1 cell cycle arrest and cell death | Leukemia. 2018 May;32(5):1147-1156. |
| PBMCs | 150 nM | 4 days | To analyze the effects of IL-7 on the proliferation of CD28- CTLs and changes in related subpopulations, results showed that Tofacitinib significantly inhibited the effects of IL-7 on CD4+CD28- CTLs and CD8+CD28- CTLs. | Front Immunol. 2022 Jul 7;13:922307. |
| CD3+ peripheral T cells | 10-500 nM | 3 days | Tofacitinib dose-dependently inhibited T cell proliferation | Cell Mol Gastroenterol Hepatol. 2022;13(2):383-404. |
| CD14+ monocytes | 500 nM | 24 h | Tofacitinib suppressed pro-inflammatory cytokine production and induced the anti-inflammatory cytokine IL-10 | Cell Mol Gastroenterol Hepatol. 2022;13(2):383-404. |
| Administration | Dosage | Frequency | Description | References | ||
| Mice | Tuberculosis model | Oral | 30 mg/kg | Twice daily for 6 months | To evaluate the acceleration of TB treatment with Tofacitinib as an adjunctive therapy. Results showed that BALB/c mice achieved apparent sterilization of the lungs at 16 weeks, while the standard treatment group required 24 weeks. C3HeB/FeJ mice showed no improvement. | EBioMedicine. 2015 Jul 14;2(8):868-73. |
| C3H/HeJ mice | AA model | Subcutaneous osmotic pump | 15 mg/kg | Once daily for 12 weeks | Tofacitinib prevented the development of AA and blocked the expansion of CD8+NKG2D+ T cells | Nat Med. 2014 Sep;20(9):1043-9. |
| NOD/SCID mice | NK-S1 subcutaneous xenograft model | Intraperitoneal injection | 25 or 50 mg/kg | 14 consecutive days | Evaluated the anti-tumorigenic potential of PRN371 in NKTL, showing significant tumor growth inhibition | Leukemia. 2018 May;32(5):1147-1156. |
| Mice | Pdcd1−/− mice | Intraperitoneal injection | 15 mg/kg | Once daily for 3 days | Tofacitinib significantly reduced KLRG1+ ILC-2 cell numbers and IL-13 cytokine production in the lungs. | J Exp Med. 2017 Jun 5;214(6):1663-1678 |
| Mice | DSS-induced colitis model | Oral | 30 mg/kg | Twice daily, starting from day 4 until the end of the experiment | Tofacitinib significantly ameliorated DSS-induced colitis, reducing histological inflammation severity and fecal inflammatory marker lipocalin 2 | Cell Mol Gastroenterol Hepatol. 2022;13(2):383-404. |
| Dose | Rat: 5 mg/kg - 50 mg/kg[3] (i.v.), 10 mg/kg - 100 mg/kg[4] (p.o.) Mice: 1 mg/kg - 100 mg/kg[5] (p.o.) |
| Administration | i.v., p.o. |
| 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 << |
| 计算器 | ||||
| 存储液制备 | ![]() |
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 |
|
| CAS号 | 540737-29-9 |
| 分子式 | C22H28N6O8 |
| 分子量 | 504.49 |
| SMILES Code | O=C(CC#N)N1C[C@H](N(C2=C3C(NC=C3)=NC=N2)C)[C@H](C)CC1.O=C(CC(C(O)=O)(O)CC(O)=O)O |
| MDL No. | MFCD11616529 |
| 别名 | 柠檬酸托法替尼 ;Tasocitinib citrate; CP-690550 citrate; CP 690,550; Tofacitinib (citrate) |
| 运输 | 蓝冰 |
| InChI Key | SYIKUFDOYJFGBQ-YLAFAASESA-N |
| Pubchem ID | 10174505 |
| 存储条件 |
In solvent -20°C: 3-6个月 -80°C: 12个月 Pure form Sealed in dry, 2-8°C |
| 溶解方案 |
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 以下溶解方案都请先按照体外实验的方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议现用现配,当天使用; 以下溶剂前显示的百分比是指该溶剂在终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶
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