Tofacitinib citrate | CAS:540737-29-9 | Manufacturer ChemFaces

Tofacitinib citrate

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Description:

Tofacitinib citrate (CP-690550 citrate) is a novel inhibitor of JAK with IC50 of 1 nM, 20 nM and 112 nM against JAK3, JAK2, and JAK1, respectively. Tofacitinib citrate has anti-infection activity.

Targets:

JAK1/JAK2/JAK3

In vivo:

J Leukoc Biol,2004 Dec;76(6):1248-55.

The JAK3 inhibitor CP-690550 selectively reduces NK and CD8+ cell numbers in cynomolgus monkey blood following chronic oral dosing.[Pubmed: 15371489]

Janus kinase 3 (JAK3) is a cytoplasmic tyrosine kinase associated with the common gamma chain, an integral component of cytokine receptors of the interleukin (IL)-2 family, including IL-4, -7, -9, -15, and -21. CP-690550 is a JAK3 inhibitor with immunosuppressive properties under development for transplantation.
METHODS AND RESULTS:
We evaluated alterations in circulating lymphocyte subsets in cynomolgus monkey blood following chronic (3-week), oral CP-690550 administration. Natural killer (NK) and CD8+ T cell numbers were reduced in a dose- and time-dependent manner; the latter was a primary effect on memory subsets. CD4+ T and B cell numbers were unaffected or slightly increased, respectively. NK cell numbers were reduced approximately 80% (vs. 35% in vehicle-treated animals) and returned to baseline levels within 3 weeks following treatment cessation. CD8+ T cells declined by a maximum 43% (vs. 25% for vehicle-treated animals) but rebounded significantly (300%) within 2 weeks after the last dose. Although CP-690550 did not result in reduction of CD4+ T cell number, these cells also increased (225%) within 2 weeks of treatment cessation. IL-15 is important for maintaining homeostasis of these cell types, and CP-690550 inhibited IL-15-induced CD69 expression in NK cells [inhibitory concentration 50% (IC50)=48.0+/-8.4 nM] and CD8+ T cells (IC50=16.2+/-1.5 nM).

Tofacitinib citrate Description

Source:
Solvent:	Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.
Storage:	Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C). Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour. Need more advice on solubility, usage and handling? Please email to: service@chemfaces.com
After receiving:	The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.

Kinase Assay:

J Med Chem,2010 Dec 23;53(24):8468-84.

Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection.[Pubmed: 21105711]

The JAK1, JAK2, and JAK3 kinase assays utilize a protein expressed in baculovirus-infected SF9 cells (a fusion protein of GST and the catalytic domain of human JAK enzyme) purified by affinity chromatography on glutathione−Sepharose. The substrate for the reaction is polyglutamic acid-tyrosine [PGT (4:1)], coated onto Nunc Maxi Sorp plates at 100 μg/mL overnight at 37 °C. The plates are washed three times, and JAK enzyme is added to the wells, which contained 100 μL of kinase buffer (50 mM HEPES, pH 7.3, 125 mM NaCl, 24 mM MgCl2) + ATP + 1 mM sodium orthovanadate). For Tofacitinib citrate, it is also added for kinase assay at different doses. After incubation at room temperature for 30 min, the plates are washed three times. The level of phosphorylated tyrosine in a given well is determined by standard ELISA assay utilizing an anti-phosphotyrosine antibody.

Cell Research:

Cancer Sci,2008 Jun;99(6):1265-73.

The JAK kinase inhibitor CP-690,550 suppresses the growth of human polycythemia vera cells carrying the JAK2V617F mutation.[Pubmed: 18482053]

Cell lines:FDCP-EpoR JAK2WT and JAK2V617F cell lines
Concentrations: 0-4 μM
Incubation Time: 72 hours
Method:
Determination of growth inhibition by Tofacitinib citrate is performed using identical culture conditions for both FDCP-EpoR JAK2WT and JAK2V617F cell lines. Briefly, 1 × 105 cells/mL are cultured in 96-well flat-bottom plates at 37 °C in a humidified 5% CO2 atmosphere using RPMI 1640 supplemented with 1.25% FCS, and 5% WEHI supernatant. Decreased FCS concentration is necessary to prevent binding between Tofacitinib citrate and serum proteins. Growth inhibition assays are terminated by addition of 20 μL CellTiter96 One Solution Reagent. Flat-bottom plates are incubated for an additional 3 hours for MTT assay. Absorbance is determined at 595 nm on a BioTek Synergy-HT microplate reader. Results are the average standard deviation of three independent determinations.

Product Name	Tofacitinib citrate
Price:
CAS No.:	540737-29-9
Catalog No.:	CFN60039
Molecular Formula:	C₁₆H₂₀N₆O.C₆H₈O₇
Molecular Weight:	504.49 g/mol
Purity:	>=98%
Type of Compound:	Alkaloids
Physical Desc.:	Powder
Source:
Solvent:	Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.
Download:	COA MSDS
Similar structural:	Comparison
Guestbook:

Size /Price /Stock	10 mM * 100 uL in DMSO / Inquiry / In-stock 10 mM * 1 mL in DMSO / Inquiry / In-stock
Related Libraries	Alkaloids Compound Library

	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

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