Tofacitinib (CP-690550,Tasocitinib) Licensed by Pfizer

Catalog No.S2789

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.

Price Stock Quantity  
USD 91 In stock
USD 70 In stock
USD 90 In stock
USD 270 In stock
USD 370 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Tofacitinib (CP-690550,Tasocitinib) Chemical Structure

Tofacitinib (CP-690550,Tasocitinib) Chemical Structure
Molecular Weight: 312.37

Validation & Quality Control

Cited by 34 publications:

6 customer reviews :

Quality Control & MSDS

Related Compound Libraries

JAK Inhibitors with Unique Features

Product Information

  • Compare JAK Inhibitors
    Compare JAK Products
  • Research Area
  • Inhibition Profile
  • Combination Therapy
    Combination Therapy

Product Description

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)

 View  More

IC50 1 nM 20 nM 112 nM 3.4 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
CD4+ T NGfadnVHfW6ldHnvckBCe3OjeR?=NWLuTXlyOjBxMUCwM|UxOCCwTR?=MkPCOFghcA>?Ml;MbY5pcWKrdIOgeIhmKGyndnXsd{Bw\iBiSVytOEwhUU[QLd8zMEBKVC1zN1GgZY5lKEmOLUKyNIn3UIUzOTh6NEW4NC=>
CD4+ T M{jPeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MlG3NVAxNzVyMDDuUS=>NHPHSGE1QCCqNWH4T3hIcW6qaXLpeJMh[W62aT3DSFMucW6mdXPl[EBETDRtwrDUJINmdGxicILvcIln\XKjdHnvci=>MYKyNVg5PDV6MB?=
CD4+ T Mo\iSpVv[3Srb36gRZN{[Xl?NFvMZYgyODBibl2=MX2yOE81QCCqNIDvW2Fi[nKxZ3H0[ZMhS0R|LXnu[JVk\WRicHjvd5Bpd3K7bHH0bY9vKG:oIGPURXR{MW[yNVg5PDV6MB?=
T cellsM4XyXGZ2dmO2aX;uJGF{e2G7M2S2TlAvOS9yLkOvNUDPxE1?MWOyOEBpNYL6NJZQ\Gm|coXweJMh|rOlLXPoZYlvKGO7dH;rbY5mKHOrZ37hcIlv\w>?MX[yNVM5OzJ2MR?=

... 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]
Features

Protocol(Only for Reference)

Kinase Assay:

[1]

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 Assay:

[1]

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.

Animal Study:

[1]

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

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Changelian PS, et al, Science, 2003, 302(5646), 875-878.

[2] Kdlacz E, et al, Am J Transplant, 2004, 4(1), 51-57.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-06-18)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02592434 Not yet recruiting Juvenile Idiopathic Arthritis Pfizer May 2016 Phase 3
NCT02321930 Recruiting Rheumatoid Arthritis University of California, Los Angeles January 2016 Phase 4
NCT02535689 Not yet recruiting Systemic Lupus Erythematosus National Institute of Arthritis and Musculoskeletal and S  ...more National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)|National Institutes of Health Clinical Center (CC) August 2015 Phase 1
NCT02487433 Completed Healthy Pfizer June 2015 Phase 1
NCT02566967 Recruiting Rheumatoid Arthritis Norman B. Gaylis, MD|Arthritis & Rheumatic Disease Specia  ...more Norman B. Gaylis, MD|Arthritis & Rheumatic Disease Specialties Research May 2015 Phase 3

view more

Chemical Information

Download Tofacitinib (CP-690550,Tasocitinib) SDF
Molecular Weight (MW) 312.37
Formula

C16H20N6O

CAS No. 477600-75-2
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 62 mg/mL warming (198.48 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/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 Name 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile

Customer Product Validation(6)


Click to enlarge
Rating
Source Cancer Discov 2012 2(7), 591-7. Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck
Method Western blot
Cell Lines NK-S1, KHYG-1 cells
Concentrations 0-2 uM
Incubation Time 48 h
Results To further confirm the involvement of JAK/STAT signaling in the survival of NKTCLs, we next evaluated the effect of a pan-JAK inhibitor, CP-690550, in NK-S1, KHYG-1, and K562 cells. As expected, both the NK-S1 and KHYG-1 cells showed a reduction of phosphorylated STAT5.

Click to enlarge
Rating
Source Blood 2012 120(4), 709-19. Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck
Method Western blot
Cell Lines AE cells
Concentrations 2, 10 uM
Incubation Time 24 h
Results Using pharmacologic inhibition, it observed Bcl-xL protein down-regulation in response to JAK2 inhibition by CP690550 and PI3K/Akt inhibition by LY294002, but not MEK inhibition by PD98059 treatment, suggesting that the PI3K/Akt pathway, but not the MEK/Erk pathway, plays a role in Bcl-xL protein regulation.

Click to enlarge
Rating
Source J Biol Chem 2012 287(41), 34825-35. Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck
Method ChIP assays
Cell Lines BMDM
Concentrations 0.1-10 uM
Incubation Time 30 min
Results In the present study, the importance of the positive feedback loop was demonstrated by blocking it with the potent and specific Janus kinase (JAK) inhibitors, Ruxolitinib or Tofacitinib, which prevent the phosphorylation of STAT1 at Tyr-701 catalyzed by JAKs.

Click to enlarge
Rating
Source PLoS One 2014 9(11), e112014. Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck
Method Crystal violet staining
Cell Lines A549 cells
Concentrations 0-4 uM
Incubation Time 2 days
Results At 48 hours post-infection titers of BUNΔNSs were ~ 5logs greater in the presence of Ruxolitinib, Tofacitinib, AZD1480 and TPCA-1 compared to DMSO treatment.

Click to enlarge
Rating
Source Arthritis Rheumatol 2014 66(1), 121-9. Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck
Method TRAP Staining
Cell Lines TRAP-positive multi-nucleated cells
Concentrations 10, 30, 100 nM
Incubation Time 2 days
Results Tofacitinib was recently shown to be effective in the treatment of RA. In fact, it demonstrated that the in vitro addition of 10-100 n M tofacitinib inhibited the multinucleation of precursor cells.

Click to enlarge
Rating
Source Tofacitinib (CP-690550,Tasocitinib) purchased from Selleck
Method NHE (Na+/H+ exchanger) activity assay
Cell Lines mouse embryos
Concentrations 1 uM
Incubation Time 30 min
Results AG-490 (40uM) significantly inhibited the pHi increase elicited by cell volume decrease in 2-cell embryos compared to that in control embryos (Fig. 4C,D), while Jak inhibitor I (1uM) and CP690550 (1uM) exhibited similar levels of inhibition (Fig. 4D).

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related JAK Products

  • FLLL32

    FLLL32 is a potent JAK2/STAT3 inhibitor with IC50 of <5 μM.

  • Cerdulatinib (PRT062070, PRT2070)

    Cerdulatinib (PRT-062070) is an oral active, multi-targeted tyrosine kinase inhibitor with IC50 of 12 nM/6 nM/8 nM/0.5 nM and 32 nM for JAK1/JAK2/JAK3/TYK2 and Syk, respectively. Also inhibits 19 other tested kinases with IC50 less than 200 nM.

  • Ruxolitinib (INCB018424)

    Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3.

  • Tofacitinib (CP-690550) Citrate

    Tofacitinib (CP-690550) Citrate 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.

  • AZD1480

    AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM in a cell-free assay, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1.

  • Fedratinib (SAR302503, TG101348)

    Fedratinib (SAR302503, TG101348) is a selective inhibitor of JAK2 with IC50 of 3 nM in cell-free assays, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. Phase 2.

  • Momelotinib (CYT387)

    Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Phase 3.

  • WP1066

    WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. Phase 1.

    Features:Similar to its parent compound AG490, WP1066 inhibits the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein.

  • Baricitinib (LY3009104, INCB028050)

    Baricitinib (LY3009104, INCB028050) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. Phase 3.

Recently Viewed Items

Tags: buy Tofacitinib (CP-690550,Tasocitinib) | Tofacitinib (CP-690550,Tasocitinib) supplier | purchase Tofacitinib (CP-690550,Tasocitinib) | Tofacitinib (CP-690550,Tasocitinib) cost | Tofacitinib (CP-690550,Tasocitinib) manufacturer | order Tofacitinib (CP-690550,Tasocitinib) | Tofacitinib (CP-690550,Tasocitinib) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us