Tofacitinib Citrate

SKU: orb1305543

Description

Tofacitinib citrate is a potent and cell-permeable Janus kinase (JAK) inhibitor with selectivity for JAK1, JAK2, and JAK3. It is widely used in both in vitro and in vivo research to investigate JAK-STAT signaling pathways in immunology, inflammation, and autoimmune disease models.

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Infectious Disease & Virology, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 540737-29-9
• MW: 504.49
• Purity: 99.75%
• Formula: C₂₂H₂₈N₆O₈
• SMILES: OC(=O)CC(O)(CC(O)=O)C(O)=O.C[C@@H]1CCN(C[C@@H]1N(C)c1ncnc2[nH]ccc12)C(=O)CC#N
• Target: Antibacterial,Influenza Virus,Antifungal,JAK,Apoptosis
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.96 mM);DMSO:55 mg/mL (109.02 mM)

Bioactivity

• Target IC50:
  ROCK2:3400 nM|Lck:3870 nM|JAK2:20 nM (cell free)|JAK1:112 nM (cell free)|JAK3:1 nM (cell free)
• In Vivo:
  CP-690,550 treatment significantly prolonged graft survival as compared to vehicle. Four of 12 animals dosed with CP-690,550 (two from each dose group) survived to study termination with normal renal function and mild rejection as determined by histopathology . Monotherapy of mice with tofacitinib quells Ab responses to an immunotoxin derived from the bacterial protein Pseudomonas exotoxin A, as well as to the model Ag keyhole limpet hemocyanin. Thousand-fold reductions in IgG1 titers to both Ags were observed 21 d post immunization. Tofacitinib treatment led to reduced numbers of CD127+ pro-B cells .
• In Vitro:
  Although Tofacitinib (CP-690,550) was highly potent for JAK3 inhibition (enzyme inhibitory potency of 1 nM), it was 20- to 100-fold less potent for JAK2 and JAK1, respectively. CP-690,550 inhibited IL-2-induced proliferation with 30-fold greater potency than its effects on GM-CSF-induced proliferation. CP-690,550 demonstrated potent inhibition in the mixed lymphocyte reaction using murine, monkey, or human cells. Consistent with its mechanism of action, these cellular activities correlated with the ability of CP-690,550 to block IL-2-induced phosphorylation of JAK3 and one of its key substrates, STAT5 . CP-690,550 treatment of murine factor-dependent cell Patersen-erythropoietin receptor (FDCP-EpoR) cells harboring human wild-type or V617F JAK2 resulted in inhibition of cell proliferation with an IC50 of 2.1 microM and 0.25 microM, respectively. CP-690,550 treatment of ex-vivo-expanded erythroid progenitors from JAK2(V617F)-positive PV patients resulted in specific, antiproliferative (IC50: 0.2 microM) and pro-apoptotic activity . The pharmacological inhibition of JAK3 by tofacitinib synergistically enhanced the antitumor effects of IMA in CML cells .
• Cell Research:
  Apoptotic cells were detected by flow cytometry using recombinant human Annexin-V conjugated with allophycocyanin. Briefly, after exposure to CP-690,550 for different periods of time, cells were washed in Ca2+-free PBS and resuspended in 100 μL of binding buffer (10 mM HEPES pH 7.4; 0.15 M NaC1; 5 mM KCl; 1 mM MgCl2; 1.8 mM CaCl2) to which Annexin-V-APC had been previously added. Cells were incubated for 20 min in the dark at room temperature, washed and resuspended in 0.3 mL binding buffer. Cells were analyzed on a FACSCalibur flow cytometer equipped with the Cell Quest Pro software .
• Animal Research:
  Mice received tofacitinib in PEG300 (100 mg/ml) or vehicle alone (PEG300) by osmotic pump infusion (Alzet Model 2004, 0.25 μl/hour, 28 days). Four days prior to immunization, mice were anesthetized and their dorsal surface was shaved. A one cm incision was made on the back to create a subcutaneous pocket and insert the pump. The incision site was closed with wound clips. Mice were injected weekly (i.p.) with SS1P recombinant immunotoxin (RIT; 5 μg/mouse) beginning on day 0; control mice received injections of saline alone. Every week before SS1P or vehicle immunization, ~50 μl of blood was drawn to obtain serum samples. Sera were stored at 80°C until analyzed .

Storage & Handling

• Storage: store at low temperature,keep away from moisture,keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Tofacitinib, Tofacitinib (CP-690550) Citrate, Tofacitinib Citrate, Tasocitinib, Tasocitinib citrate, Tasocitinib Citrate, JAK1, JAK2, JAK, Janus kinase, JAK3, inhibit, InfluenzaVirus, Influenza Virus, Fungal, Inhibitor, CP690550, CP-690550, CP690550 Citrate, CP-690550 Citrate, CP-690550 citrate, CP 690550, CP 690550 Citrate, Apoptosis, Bacterial

Compound Identifiers

PubChem CID

10174505