Tofacitinib (CP-690550) citrate
Supplier: 0000018453
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Warning
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Synonyms:
(3R,4R)-4-Methyl-3-(methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-β-oxo-1-piperidinepropanenitrile citrate, 3-((3R,4R)-4-Methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile 2-hydroxypropane-1,2,3-tricarboxylate, Tofacitinib citrate
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.
Biological activity - In vitro:
Tofacitinib citrate inhibits IL-2-mediated human T cell blast proliferation and IL-15-induced CD69 expression with IC50 of 11 nM and 48 nM, respectively. Tofacitinib citrate prevents mixed lymphocyte reaction with IC50 of 87 nM. Tofacitinib citrate treatment of murine factor-dependent cell Patersen–erythropoietin receptor (FDCP-EpoR) cells harboring human wild-type or V617F JAK2 leads to prevention of cell proliferation with IC50 of 2.1 µM and 0.25 µM, respectively. Tofacitinib citrate inhibits interleukin-6-induced phosphorylation of STAT1 and STAT3 with IC50 of 23 nM and 77 nM, respectively. Moreover, Tofacitinib citrate generates a significant pro-apoptotic effect on murine FDCP-EpoR cells carrying JAK2VV617F, whereas a lesser effect is observed for cells carrying wild-type JAK2. This activity is coupled with the inhibition of phosphorylation of the key JAK2V617F-dependent downstream signaling effectors signal transducer and activator of transcription (STAT)3, STAT5, and v-akt murine thymoma viral oncogene homolog (AKT). Additionally, tofacitinib citrate prevents IL-15-induced CD69 expression in human and cynomolgus monkey NK and CD8+ T cells in vitro.
Biological activity - In vivo:
Tofacitinib citrate decrease a delayed-type hyper-sensitivity response and extended cardiac allograft survival in murine models. Furthermore, tofacitinib citrate treatment of ex-vivo-expanded erythroid progenitors from JAK2V617F-positive PV patients results in specific, antiproliferative (IC50=0.2 μM) and pro-apoptotic activity. In contrast, expanded progenitors from healthy controls are less sensitive to Tofacitinib citrate in proliferation (IC50>1.0 μM), and apoptosis assays. During 2 weeks of tofacitinib citrate dosing at 10 and 30 mg/kg/d, a significant, time-dependent decrease in NK cell numbers relative to vehicle treatment is observed. Effector memory CD8+ cell numbers in the Tofacitinib citrate-treated group are 55% less than those observed in animals treated with vehicle.
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Formula:
C₁₆H₂₀N₆O·C₆H₈O₇ Storage Temperature: Freezer |
MDL Number:
MFCD11616529 CAS Number: 540737-29-9 UN: 3077 ADR: 9,III |
Specification Test Results
| Purity (HPLC) | 99.89% |
| NMR | Consistent with Structure |
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