Tofacitinib

SKU: orb1300872

Description

Tofacitinib (Tasocitinib) is an orally bioavailable Janus kinase (JAK) inhibitor with selectivity for JAK3, JAK2, and JAK1. It is a research compound applied in studies of rheumatoid arthritis and other immune-mediated diseases, utilizing both in vitro cellular assays and in vivo animal models to investigate JAK-STAT signaling pathways.

Research Area

Immunology & Inflammation

Key Properties

• CAS Number: 477600-75-2
• MW: 312.4
• Purity: >98%
• Formula: C₁₆H₂₀N₆O
• SMILES: C[C@@H]1CCN(C[C@@H]1N(C)C1=C2C=CNC2=NC=N1)C(=O)CC#N
• Target: Kinase
• Solubility: Soluble in DMSO (up to 100 mg/ml) or in Ethanol (up to 100 mg/ml).

Bioactivity

• Target IC50:
  Lck:3870 nM|ROCK2:3400 nM|JAK3:1 nM|JAK2:20 nM|JAK1:112 nM
• In Vivo:
  METHODS: To detect anti-tumor activity in vivo, NSG mice bearing in situ-diffused MM.1S xenografts were injected subcutaneously with Tofacitinib (21.5 mg/kg, 50% DMSO+10% PEG 400+40% water) once daily for four weeks. RESULTS: Mouse survival was significantly improved and tumor load was significantly reduced based on bioluminescence imaging quantification.
• In Vitro:
  METHODS: The human MM cell line MM.1S was co-cultured with the immortalized BMSC lines HS5 and HS27A and treated with Tofacitinib (0-10 µM) for 24 h. Cell viability was measured by CellTiter-Glo reagent. RESULTS: A significant increase in MM.1S cell number was observed compared to monoculture growth, confirming the stroma-induced proliferative signaling in this cell line.Tofacitinib treatment reduced MM.1S cell number in a dose-dependent manner.Tofacitinib alone had no effect on MM.1S cell viability or on stromal cells alone. METHODS: NK-92 cells were treated with Tofacitinib (50 nM) overnight and IL-15 (2.33 nM) for 2 h. STAT1 phosphorylation was measured. RESULTS: Tofacitinib blocked IL-15 signaling in NK-92 cells. tofacitinib disrupted JAK/STAT signaling by blocking STAT protein phosphorylation.
• Cell Research:
  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 10 mg/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. (Only for Reference)

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Tasocitinib; CP-690550

Compound Identifiers

PubChem CID

9926791