Tofacitinib (CP-690550,Tasocitinib)

Licensed by Pfizer Catalog No.S2789

Tofacitinib (CP-690550,Tasocitinib) Chemical Structure

Molecular Weight(MW): 312.37

Tofacitinib (CP-690550,Tasocitinib) is a novel inhibitor of JAK3 with IC50 of 1 nM in cell-free assays, 20- to 100-fold less potent against JAK2 and JAK1.

Size Price Stock Quantity  
In DMSO USD 91 In stock
USD 70 In stock
USD 90 In stock
USD 270 In stock
USD 370 In stock

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Cited by 34 Publications

6 Customer Reviews

  • Effects of CP-690550 on NKTCL cell lines. NK-S1, KHYG-1 cells were treated with CP-690550 for 48 hours, and the effect on STAT5 phosphorylation was evaluated by Western blotting.

    Cancer Discov 2012 2(7), 591-7. Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck.

    AE cells were treated with vehicle control (DMSO), a MEK inhibitor (PD98059), a PI3K inhibitor (LY294002) or a JAK2 inhibitor (CP690550) at indicated concentrations for 24 hours, followed by lysis for immunoblotting.

    Blood 2012 120(4), 709-19. Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck.

  • BMDM from wild time mice were incubated with the concentrations of Ruxolitinib (R) or Tasocitinib (T) indicated, then stimulated for 30 min with (+) or without (-) 500 units/ml IFNβ. The cells were lysed and 30 ug of cell extract protein subjected to SDS-PAGE and immunoblotted with an antibody that recognizes STAT1 phosphorylated at Tyr-701 (p-STAT1) and an antibody that recognizes all forms of STAT1.

    J Biol Chem 2012 287(41), 34825-35. Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck.

    Effect of a panel of IFN inhibitors on BUNΔNSs virus growth in A549 cells. The inhibitor panel consists of small molecules that target the IKK2 (TPCA-1) and TBK1 (BX795, MRT6884, MRT6707) components of the IFN induction pathway and JAK1 (Cyt387, AZD1480, Ruxolitinib, Tofacitinib) a component of the IFN signaling pathway. Effect of the inhibitors was compared with A549 cells constitutively expressing viral IFN antagonists that block IFN production (BVDV-Npro) or IFN signaling (PIV5-V). Effect of various inhibitor concentrations on plaque size formation. Plaques were visualized 2 days post-infection by crystal violet staining.

    PLoS One 2014 9(11), e112014. Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck.

  • TRAP-positive multinucleated cell differentiation depends on JAK and is inhibited by tofacitinib in vitro. Effect of tofacitinib on the differentiation of TRAP-positive multi-nucleated cells in vitro (n =3 wells/experiment). Original magnification x 100.

    Arthritis Rheumatol 2014 66(1), 121-9. Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck.

     

    Role of tyrosine kinase Jak2 in NHE1 activation. Mean (WSEM) pHi increases upon introduction of 350mOsM medium with AG490 (example shown in C), Jak Inhibitor I (Jak Inhibit I; 1uM), CP690550 (1uM), and control (vehicle alone, with 0.1% ethanol for AG490, 0.01% DMSO for Jak Inhibitor I and CP690550). Bars that do not share the same letter are significantly different by one-way ANOVA and Tukey–Kramer Multiple Comparisons Test (P < 0.05).

    Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck.

Purity & Quality Control

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description Tofacitinib (CP-690550,Tasocitinib) is a novel inhibitor of JAK3 with IC50 of 1 nM in cell-free assays, 20- to 100-fold less potent against JAK2 and JAK1.
Targets
JAK3 [1]
(Cell-free assay)
JAK2 [1]
(Cell-free assay)
JAK1 [1]
(Cell-free assay)
ROCK2 [1]
(Cell-free assay)
LCK [1]
(Cell-free assay)
1 nM 20 nM 112 nM 3.4 μM 3.87 μM
In vitro

CP-690550 is a specific, orally inhibitor of JAK3, it is 20- to 100-fold less potent for JAK2 and JAK1 with IC50 of 20 nM and 112 nM, respectively. CP-690550 doesn't have potent activity against 30 other kinases (all median IC50 > 3000 nM). CP-690,550 inhibits IL-2–induced proliferation with 30-fold greater potency than its effects on GM-CSF–induced proliferation. [1] CP-690550 effectively inhibits a murine mixed lymphocyte reaction (MLR) (IC50 = 91 nM). [2] CP-690550 potently inhibits IL-4 induced upregulation of CD23 (IC50=57 nM) and class II major histocompatibility complex (MHCII) expression (IC50=71 nM) on murine B cells. [3] A recent research indicates low dose of CP-690550 accelerates the onset of experimental autoimmune encephalomyelitis by potentiating Th17 differentiation. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CD4+ T  MmL4SpVv[3Srb36gRZN{[Xl? NWraS2R[OjBxMUCwM|UxOCCwTR?= MX:0PEBp MX;pcohq[mm2czD0bIUhdGW4ZXzzJI9nKCCLTD20MEBKTk5vzsOsJGlNNTF5QTDhcoQhUUxvMkK= NIP6[oczOTh6NEW4NC=>
CD4+ T  NVPCfplXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoDxNVAxNzVyMDDuUS=> Mon4OFghcA>? NWjSXpU5cW6qaXLpeJMh[W62aT3DSFMucW6mdXPl[EBETDRtwrDUJINmdGxicILvcIln\XKjdHnvci=> Ml;oNlE5QDR3OEC=
CD4+ T  NHL6SJpHfW6ldHnvckBCe3OjeR?= NILqfIUyODBibl2= NUjpcZdKOjRxNEigbC=> NXj1SJZp[WK{b3fheIV{KEOGMz3pcoR2[2WmIIDoc5NxcG:{eXzheIlwdiCxZjDTWGFVew>? M17Qb|IyQDh2NUiw
T cells NIPHXGRHfW6ldHnvckBCe3OjeR?= Mo\FNE4yNzBwMz:xJO69VQ>? MUKyOEBp MXvkbZNzfXC2czFOt4Mu[2ijaX6gZ5l1d2urbnWgd4lodmGuaX7n M1zrUFIyOzh|MkSx

... Click to View More Cell Line Experimental Data

In vivo In a murine model of heterotopic heart transplantation (DBA2 donor heart into C57/BL6 host), CP-690550 results in a dose-dependent increase in survival of transplanted hearts.The EC50 (drug concentration in blood at which 50% of mice will maintain their graft for >28 days) to be ~60 ng/mL.CP-690550 prevents rejection of allogeneic kidneys in nonhuman primate (NHPs, macaca fascicularis) (MST of 62 and 83 days for the 50 to 100 ng/ml groups and 200 to 400 ng/ml groups, respectively). [1] Mice chronically dosed with CP-690550 (1.5-15 mg/kg/day) demonstrates dose and time-dependent alterations in lymphocyte subsets when examined by flow cytometry. The most dramatic change observed is a 96% reduction in splenic NK1.1+TCRb-cell numbers following 21 days of treatment. Delayed-type hypersensitivity (DTH) responses in sensitized mice are reduced in a dose-dependent manner following treatment with CP-690550 (1.87–30 mg/kg, s.c.). Extended survival of neonatal Balb/c hearts implanted into the ear pinna of MHC mismatched C3H/HEN mice is observed with CP-690550 monotherapy (10–30 mg/kg/day), but improved upon combination with cyclosporin (10 mg/kg/day). [2]

Protocol

Kinase Assay:

[1]

+ Expand

JAK3 Kinase Assay:

A fragment encoding the catalytic domain of human JAK3 (785aa to 1125aa, JH1 catalytic domain) is amplified by PCR from the full length cDNA and cloned into the EcoRI site of the baculovirus transfer vector pVL1393. Recombinant baculovirus is used to infect Sf9 (Spodoptera frugipedra) cells and recombinant GSTJAK3 fusion protein is isolated on glutathione sepharose. The fusion protein is eluted with reduced glutathione and stored in buffer containing 50 mM Tris, pH 7.5, 10 mM DTT and 10% glycerol. JAK3 kinase activity is measured by ELISA as follows: Plates are coated overnight with a random L-glutamic acid and tyrosine co-polymer (4:1) (100 ug/mL). The plates are washed and recombinant JAK3 JH1:GST (100 ng/well) with or without inhibitors is incubated at room temperature for 30 minutes, after which HRP-conjugated PY20 anti-phosphotyrosine antibody (ICN) is added and developed by TMB (3,3',5,5'-tetramethylbenzidine). Other kinases (Table 1) are produced in E. coli or in insect cells, depending upon what is found to be optimal for the given kinase. The catalytic activity of tyrosine kinases is easured using the aftorementioned ELISA, whereas serine/threonine kinases are assayed using radioactive enzyme assays.
Cell Research:

[1]

+ Expand
  • Cell lines: Human T blasts cell
  • Concentrations: 0-4000 nM
  • Incubation Time: 4 days
  • Method:

    To measure IL-2-dependent proliferation, isolated lymphocytes are resuspended to a cell density of 1-2 × 106/mL in complete RPMI medium (RPMI 1640 containing 10% (w/v) fetal calf serum (FCS), 1%(w/v) penicillin and treptomycin).Phytohemagluttinin (PHA) is added to a final concentration of 10mg/mL, and the culture incubated for 3 days at 37 °C in a humidified 5% (v/v) CO2 incubator to upregulate IL-2R and JAK3 expression. IL-2 (200U/mL), with or without CP-690,550 is then added and the cells are incubated for 72 hours at 37 °C in a humidified 5% (v/v) CO2 incubator, after which 50 mL of 3H-thymidine (5mCi/mL) is added. The plates are incubated for an additional 18 hours, harvested with a 96-well harvester, and counted on a scintillation counter. HUO3 cells are maintained in culture with granulocyte-macrophage colony stimulating factor and human foreskin fibroblasts are maintained in culture with 10% fetal calf serum. CP-690550 is added to freshly plated cells and cultured for 4 days. 3Hthymidine is added during the last 18 hours of the culture period.


    (Only for Reference)
Animal Research:

[1]

+ Expand
  • Animal Models: DBA/2 and C57/BL6 mice
  • Formulation: CP-690550 is dissolved in polyethylene glycol 300.
  • Dosages: 0-136 ng/mL
  • Administration: Administered via osmotic minipump infusion
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 62 mg/mL (198.48 mM) warming
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 2% DMSO+30% PEG 300+ddH2O 5mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 312.37
Formula

C16H20N6O

CAS No. 477600-75-2
Storage powder
in solvent
Synonyms N/A

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02535689 Recruiting Systemic Lupus Erythematosus National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)|National Institutes of Health Clinical Center (CC) August 25, 2015 Phase 1
NCT03000439 Not yet recruiting Arthritis Juvenile Idiopathic Pfizer April 2017 Phase 3
NCT03002649 Recruiting Dermatomyositis Johns Hopkins University|Pfizer January 2017 Phase 1
NCT03011281 Recruiting Rheumatoid Arthritis Hanyang University November 2016 --
NCT02996500 Recruiting Rheumatoid Arthritis Pfizer November 2016 Phase 2
NCT02812342 Active, not recruiting Alopecia Areata|Alopecia Totalis|Alopecia Universalis Yale University September 2016 Phase 2

Tech Support

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID