Tofacitinib (CP-690550) CitratePotent JAK inhibitor CAS# 540737-29-9 |
Quality Control & MSDS
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| Cas No. | 540737-29-9 | SDF | Download SDF |
| PubChem ID | 10174505 | Appearance | Powder |
| Formula | C22H28N6O8 | M.Wt | 504.49 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | Tasocitinib citrate; CP-690550 citrate | ||
| Solubility | DMSO : 41.67 mg/mL (82.60 mM; Need ultrasonic) H2O : 3.33 mg/mL (6.60 mM; Need ultrasonic) | ||
| Chemical Name | 2-hydroxypropane-1,2,3-tricarboxylic acid;3-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile | ||
| SMILES | CC1CCN(CC1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N.C(C(=O)O)C(CC(=O)O)(C(=O)O)O | ||
| Standard InChIKey | SYIKUFDOYJFGBQ-YLAFAASESA-N | ||
| Standard InChI | InChI=1S/C16H20N6O.C6H8O7/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16;7-3(8)1-6(13,5(11)12)2-4(9)10/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20);13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t11-,13+;/m1./s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Tofacitinib (CP-690550) Citrate is a novel inhibitor of JAK3 with IC50 of 1 nM, 20- to 100-fold less potent against JAK2 and JAK1. | |||||
| Targets | JAK3 | |||||
| IC50 | 1 nM | |||||
| Cell experiment [1]: | |
| Cell lines | Naïve T cell |
| Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
| Reacting condition | 16h; 50 nM |
| Applications | A concentration of 100 nM. 50 nM, but not 10 nM, CP-690,550 suppressed IFN- c production 4 days after Th1 differentiation conditions were established, while both 10 nM and 50 nM CP-690,550 strongly suppressed IL-4 production under Th2 differentiation conditions. This suggests that CP-690,550 inhibits both Th1 and Th2 differentiation, and that Th2 is more sensitive than Th1 to this drug. We then examined the effect of CP-690,550 on Th17 and induced T regulatory (iTreg) cells. CP-690,550 enhanced IL-17 production while suppressing Foxp3 and IL-10 induction in a dose-dependent manner under Th17 differentiation conditions. These data indicate that <100 nM CP-690,550 efficiently inhibits Th1, Th2 and iTreg while promoting Th17, in vitro. |
| Animal experiment [1]: | |
| Animal models | C57BL6/J mice and DBA/1J mice |
| Dosage form | 30 nM; intraperitoneal injection |
| Application | Naïve CD4+T cells isolated from mice were stimulated with various cytokines in the presence of various concentrations of CP-690,550. CP-690,550 selectively inhibited IFN c -induced STAT1, IL-4-induced STAT6, and IL-2-induced STAT5 at 3–30 nM, while 30 nM CP-690,550 did not suppress IL-6-induced STAT3 phosphorylation. A concentration greater than 100 nM was required for the partial suppression of STAT3 |
| Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
| References: [1] Yoshida H, Kimura A, Fukaya T, et al. Low dose CP-690,550 (tofacitinib), a pan-JAK inhibitor, accelerates the onset of experimental autoimmune encephalomyelitis by potentiating Th17 differentiation[J]. Biochemical and biophysical research communications, 2012, 418(2): 234-240. | |
Tofacitinib (CP-690550) Citrate Dilution Calculator
Tofacitinib (CP-690550) Citrate Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.9822 mL | 9.911 mL | 19.822 mL | 39.644 mL | 49.555 mL |
| 5 mM | 0.3964 mL | 1.9822 mL | 3.9644 mL | 7.9288 mL | 9.911 mL |
| 10 mM | 0.1982 mL | 0.9911 mL | 1.9822 mL | 3.9644 mL | 4.9555 mL |
| 50 mM | 0.0396 mL | 0.1982 mL | 0.3964 mL | 0.7929 mL | 0.9911 mL |
| 100 mM | 0.0198 mL | 0.0991 mL | 0.1982 mL | 0.3964 mL | 0.4955 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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Tofacitinib citrate, also known as CP-690550 citrate, is a potent inhibitor of janus kinase 3 (JAK3), a hematopoetic cell-restricted tyrosine kinase involved in signal transduction regulating lymphocyte survival, proliferation, differentiation, and apoptosis. The inhibition is JAK3 specific with a selectivity 1000-fold more than other non-JAK family kinases. Besides inhibiting JAKS (IC50 = 1 nM), tofacitinib citrate also inhibits janus kinase 2 (JAK2) and janus kinase 1 (JAK1) with 20- and 100-fold less in potency respectively. However, in a recent study, the binding affinities (Ki) of tofacitinib citrate towards JAK1, JAK2, and JAK3 were reported to be 1.6 nM, 21.7 nM, and 6.5 nM respectively.
Reference
Lalitha Vijayakrishnan, R. Venkataramanan and Palak Gulati. Treating inflammation with the janus kinase inhibitor CP-690,550. Trends in Pharmacological Sciences 2011: 32 (1); 25-34
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Identification of related substances in tofacitinib citrate by LC-MS techniques for synthetic process optimization.[Pubmed:28549242]
J Pharm Biomed Anal. 2017 Sep 5;143:17-25.
A specific LC-MS method was developed for separation, identification and characterization of the process-related substances and degradation products in tofacitinib citrate. The separation was achieved on a LiChrospher C18 column (250mmx4.6mm, 5mum) by linear gradient elution of 0.1% ammonium acetate solution (pH adjusted to 4.0 by formic acid) and acetonitrile at a flow rate of 1.0mL/min. Forced degradation studies were conducted under hydrolytic (acidic, basic), oxidative, photolytic and thermal stress conditions as described in ICH. It was found that tofacitinib was stable under photolytic condition, but degraded obviously in acidic, basic, thermal and oxidative conditions. The high resolution TOF-MS and MS/MS were used for determination and structural identification of the related substances. Eleven major related substances were detected and identified as five process-related substances and six degradation products, and three of them were further synthesized and characterized by NMR spectroscopy. The most plausible mechanisms involved in the formation of the related substances were also proposed. Since related substances have a significant impact on drug safety, quality and efficacy, the data obtained are valuable for process monitoring and quality assurance of tofacitinib citrate.
Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata.[Pubmed:27699252]
JCI Insight. 2016 Sep 22;1(15):e89776.
BACKGROUND: Alopecia areata (AA) is an autoimmune disease characterized by hair loss mediated by CD8(+) T cells. There are no reliably effective therapies for AA. Based on recent developments in the understanding of the pathomechanism of AA, JAK inhibitors appear to be a therapeutic option; however, their efficacy for the treatment of AA has not been systematically examined. METHODS: This was a 2-center, open-label, single-arm trial using the pan-JAK inhibitor, tofacitinib citrate, for AA with >50% scalp hair loss, alopecia totalis (AT), and alopecia universalis (AU). Tofacitinib (5 mg) was given twice daily for 3 months. Endpoints included regrowth of scalp hair, as assessed by the severity of alopecia tool (SALT), duration of hair growth after completion of therapy, and disease transcriptome. RESULTS: Of 66 subjects treated, 32% experienced 50% or greater improvement in SALT score. AA and ophiasis subtypes were more responsive than AT and AU subtypes. Shorter duration of disease and histological peribulbar inflammation on pretreatment scalp biopsies were associated with improvement in SALT score. Drug cessation resulted in disease relapse in 8.5 weeks. Adverse events were limited to grade I and II infections. An AA responsiveness to JAK/STAT inhibitors score was developed to segregate responders and nonresponders, and the previously developed AA disease activity index score tracked response to treatment. CONCLUSIONS: At the dose and duration studied, tofacitinib is a safe and effective treatment for severe AA, though it does not result in a durable response. Transcriptome changes reveal unexpected molecular complexity within the disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT02197455 and NCT02312882. FUNDING: This work was supported by the US Department of Veterans Affairs Office of Research and Development, National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institutes of Health grant R01 AR47223 and U01 AR67173, the National Psoriasis Foundation, the Swedish Society of Medicine, the Fernstrom Foundation, the Locks of Love Foundation, the National Alopecia Areata Foundation, and the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research.
JAK inhibitors: A broadening approach in rheumatoid arthritis.[Pubmed:27722215]
Drugs Today (Barc). 2016 Aug;52(8):467-469.
Pfizer's Xeljanz (tofacitinib citrate) was the first Janus kinase (JAK) inhibitor to reach the market for rheumatoid arthritis (RA) following its U.S. approval in November 2012, and it has since gained approval in more than 45 countries as a second-line therapy for RA after failure of disease-modifying antirheumatic drugs (DMARDs). This emerging category has heralded an attractive new class of oral treatment options in RA, with a notable opportunity in patients who stop responding to DMARDs, but they are facing a challenging market. Despite RA affecting approximately 23.7 million people worldwide, Xeljanz faces a market dominated by the anti-tumor necrosis factor (anti-TNF) biologicals, which have robust long-term safety and efficacy. The availability of biosimilars of these market leaders is also intensifying competition, and a high price and uncertainty over long-term safety is currently tempering the market for the JAK inhibitors.
