[CAS NO. 477600-75-2] Tofacitinib (CP-690550)

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PRODUCTS SPECIFICATIONS [477600-75-2]

Catalog

SLK-S2789

Brand

Selleck

CAS

477600-75-2

DESCRIPTION [477600-75-2]

Overview

MDL	MFCD11035919
Molecular Weight	312.37
Molecular Formula	C16H20N6O
SMILES	N(C)(C1=C2C(NC=C2)=NC=N1)[C@H]3CN(C(CC#N)=O)CC[C@H]3C

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Description

Tofacitinib (CP-690550,Tasocitinib) is a novel inhibitor of with of 1 nM in cell-free assays, 20- to 100-fold less potent against JAK2 and JAK1. Tofacitinib inhibits the expression of antiapoptotic and in human plasmacytoid dendritic cells (PDC) and induced PDC .

Targets

JAK3 ^[1] (Cell-free assay)	JAK2 ^[1] (Cell-free assay)	JAK1 ^[1] (Cell-free assay)
1 nM	20 nM	112 nM

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. CP-690550 effectively inhibits a murine mixed lymphocyte reaction (MLR) (IC50 = 91 nM). 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. A recent research indicates low dose of CP-690550 accelerates the onset of experimental autoimmune encephalomyelitis by potentiating Th17 differentiation.

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). 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).

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.
[3] Kudlacz E, et al, Eur J harmacol, 2008, 582(1-2), 154-161.
[4] Yoshida H, et al, Biochem Biophys Res Commun, 2012, 418(2), 234-240.
[5] Borie DC, et al, Transplantation, 2005, 80(12), 1756-1764.
[6] Kudlacz E, et al. Am J Transplant, 2004, 4(1), 51-57.

Synonyms

1-Piperidinepropanenitrile, 4-methyl-3-(methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-β-oxo-, (3R,4R)-

3-Piperidinamine, 1-(cyanoacetyl)-4-methyl-N-methyl-N-1H-pyrrolo[2,3-d]pyrimidin-4-yl-, (3R,4R)-

(3R,4R)-4-Methyl-3-(methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-β-oxo-1-piperidinepropanenitrile

CP 690550

Tofacitinib