1. Epigenetics
    Stem Cell/Wnt
    JAK/STAT Signaling
  2. JAK

Tofacitinib (Synonyms: Tasocitinib; CP-690550)

Cat. No.: HY-40354 Purity: 99.96%
Handling Instructions

Tofacitinib is a JAK3/2/1 inhibitor with IC50s of 1, 20, and 112 nM, respectively.

For research use only. We do not sell to patients.

Tofacitinib Chemical Structure

Tofacitinib Chemical Structure

CAS No. : 477600-75-2

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Customer Review

Other Forms of Tofacitinib:

    Tofacitinib purchased from MCE. Usage Cited in: Pulm Pharmacol Ther. 2017 Apr;43:60-67.

    Effect of Tofacitinib administered 1 h before LPS challenge. (A) Effect of different doses of Tofacitinib on STAT3 activation in lung homogenates obtained 30 min after LPS challenge. (B) Effect of different doses of Tofacitinib on STAT3 activation in lung homogenates obtained 4 h after LPS challenge.

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    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Tofacitinib is a JAK3/2/1 inhibitor with IC50s of 1, 20, and 112 nM, respectively.

    IC50 & Target[1]

    JAK3

    1 nM (IC50)

    JAK2

    20 nM (IC50)

    JAK1

    112 nM (IC50)

    Rock-II

    3400 nM (IC50)

    Lck

    3870 nM (IC50)

    In Vitro

    Tofacitinib (CP-690550) citrate binds potentially at JAK3 and JAK2 as 2.2 nM and 5 nM (Kd). The report includes additional binding for Tofacitinib at Camk1 (Kd of 5,000 nM), DCamkL3 (Kd of 4.5 nM), Mst2 (Kd of 4,300 nM), Pkn1 (Kd of 200 nM), Rps6ka2 (Kin.Dom.2-C-terminal) (Kd of 1,400 nM), Rps6ka6 (Kin.Dom.2-C-terminal) (Kd of 1,200 nM), Snark (Kd of 420 nM), Tnk1 (Kd of 640 nM) and Tyk2 (Kd of 620 nM)[1].

    In Vivo

    Animals that are treated with Tofacitinib show a significantly lower production of anti-drug antibodies (ADAs) compare with PEG-treated control mice (for five weeks after initial immunization, p<0.01, n=8). Moreover ADAs become detectable earliest on day 28. A difference of 1000- to 200-fold in titers to SS1P is apparent from days 21 through 35, respectively. Compare to SS1P, mice injected with keyhole limpet hemocyanin (KLH) generate a more rapid antibody response. Yet, the administration of Tofacitinib reduces anti-KLH titers compare to controls (p<0.05 on day 21, p<0.01 on day 28, respectively, n=5). Reductions in titers ranged from 5000- to 250-fold from days 21 through 28, respectively[2]. Based on previous dose-response studies, a daily dose of Tofacitinib of 6.2 mg/kg is selected to provide 80% inhibition of hind paw volume and plasma exposure capable of suppressing the JAK1 and JAK3 signaling pathways for >4 hours[3].

    Clinical Trial
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 100 mg/mL (320.13 mM)

    H2O : 0.15 mg/mL (0.48 mM; Need ultrasonic and warming)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 3.2013 mL 16.0067 mL 32.0133 mL
    5 mM 0.6403 mL 3.2013 mL 6.4027 mL
    10 mM 0.3201 mL 1.6007 mL 3.2013 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 2.5 mg/mL (8.00 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (8.00 mM); Clear solution

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (8.00 mM); Clear solution

    References
    Kinase Assay
    [1]

    Kinase activity is recorded via a competition binding assay of selected kinases that are fused to a proprietary tag. Measurements of the amount of kinase binds to an immobilized, active-site directed ligand in the presence and absence of the test compound (e.g., Tofacitinib) provide a % of DMSO control for binding of ligand. Activities between 0 and 10 are selected for Kd determinations. Dendrogram representations are generated by an in-house visualization tool designated PhyloChem[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    Human CD4+ positive cells are enriched from peripheral blood mononuclear cells obtained from a healthy donor by magnetic separation (CD4+ MACS beads). CD4+ cells are activated for 3 days with plate bound anti-CD3 and anti CD28 antibodies (5 ug/mL each), and then expanded for another 4 days in the presence of IL-2 (50 U/mL). Cells are rested overnight in 1% RPMI, and pre-incubated with Tofacitinib or DMSO control for 1 hour at indicated concentrations (5 nM, 50 nM, 500 nM; DMSO concentration is equal in all preparations) and then activated with IL-2 (1000 u/mL) or IL-12 (100 ng/mL) for 15 minutes. Cells (10×106/condition) are lysed in 1% Triton-x lysis buffer and equal amounts of cell lysate are run in NuPage Bis-Tris gel (4-12% gradient). Proteins are transferred onto nitrocellulose membrane. Detection is done with indicated antibodies using Odyssey western blotting system[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2][3]

    Mice[2]
    Female BALB/c mice (6-8 weeks old) are used. Mice receive Tofacitinib in PEG300 (100 mg/mL) or vehicle alone (PEG300) by osmotic pump infusion (Alzet Model 2004, 0.25 μL/hour, 28 days). Four days prior to immunization, mice are anesthetized and their dorsal surface is shaved. A one cm incision is made on the back to create a subcutaneous pocket and insert the pump. The incision site is closed with wound clips. Mice are injected weekly (i.p.) with SS1P recombinant immunotoxin (RIT; 5 μg/mouse) beginning on day 0; control mice received injections of saline alone. Every week before SS1P or vehicle immunization, 50 μL of blood is drawn to obtain serum samples. Sera are stored at −80°C until analyzed.
    Rats[3]
    Adjuvant-induced arthritis (AIA) is induced in female Lewis rats. Rats are randomized according to hind paw volume and assigned to Tofacitinib or vehicle treatment regimens. Groups of 7-8 rats per treatment group, and normal naive rats (n=4 per group), are euthanized either 4 hours, 4 days, or 7 days after beginning treatment (days 16, 20, and 23 after immunization, respectively). Tofacitinib is suspended in 0.5% methylcellulose/0.025% Tween 20 for in vivo studies. Once-daily oral administration of vehicle or Tofacitinib (6.2 mg/kg) is initiated on day 16 following immunization and continued through day 23. Paw volumes are reassessed 4 and 7 days after the beginning of treatment (days 20 and 23 after immunization, respectively). For micro-computed tomography (micro-CT) imaging, as well as tartrate-resistant acid phosphatase (TRAP) staining in paw tissue, AIA is induced in a separate cohort of Lewis rats.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    312.37

    Formula

    C₁₆H₂₀N₆O

    CAS No.

    477600-75-2

    SMILES

    O=C(CC#N)N1C[[email protected]](N(C2=C3C(NC=C3)=NC=N2)C)[[email protected]](C)CC1

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.96%

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    Product Name:
    Tofacitinib
    Cat. No.:
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    Cat. No.: HY-40354