Tofacitinib (CP-690550)

製品コードS2789 バッチS278907

印刷

化学情報

Chemical Structure Synonyms CP-690550, Tasocitinib Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C16H20N6O
分子量 312.37 CAS No. 477600-75-2
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 62 mg/mL (198.48 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 3.100mg/ml (9.92mM) Taking the 1 mL working solution as an example, add 50 μL of 62 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Tofacitinib is a novel inhibitor of JAK3 with IC50 of 1 nM in cell-free assays, 20- to 100-fold less potent against JAK2 and JAK1. Tofacitinib inhibits the expression of antiapoptotic BCL-A1 and BCL-XL in human plasmacytoid dendritic cells (PDC) and induced PDC apoptosis.
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. This compound doesn't have potent activity against 30 other kinases (all median IC50 > 3000 nM). It inhibits IL-2–induced proliferation with 30-fold greater potency than its effects on GM-CSF–induced proliferation. [1] This chemical effectively inhibits a murine mixed lymphocyte reaction (MLR) (IC50 = 91 nM). [2] It 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. [3] A recent research indicates low dose of this compound accelerates the onset of experimental autoimmune encephalomyelitis by potentiating Th17 differentiation. [4]
in vivo In a murine model of heterotopic heart transplantation (DBA2 donor heart into C57/BL6 host), Tofacitinib 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.This compound 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). [1] Mice chronically dosed with this compound (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 this chemical (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 this compound monotherapy (10–30 mg/kg/day), but improved upon combination with cyclosporin (10 mg/kg/day). [2]

プロトコル(参考用のみ)

キナーゼアッセイ JAK3 Kinase Assay
A fragment encoding the catalytic domain of human JAK3 (785aa to 1125aa, JH1 catalytic domain) is amplified by PCR from the full length cDNA and cloned into the EcoRI site of the baculovirus transfer vector pVL1393. Recombinant baculovirus is used to infect Sf9 (Spodoptera frugipedra) cells and recombinant GSTJAK3 fusion protein is isolated on glutathione sepharose. The fusion protein is eluted with reduced glutathione and stored in buffer containing 50 mM Tris, pH 7.5, 10 mM DTT and 10% glycerol. JAK3 kinase activity is measured by ELISA as follows: Plates are coated overnight with a random L-glutamic acid and tyrosine co-polymer (4:1) (100 ug/mL). The plates are washed and recombinant JAK3 JH1:GST (100 ng/well) with or without inhibitors is incubated at room temperature for 30 minutes, after which HRP-conjugated PY20 anti-phosphotyrosine antibody (ICN) is added and developed by TMB (3,3',5,5'-tetramethylbenzidine). Other kinases (Table 1) are produced in E. coli or in insect cells, depending upon what is found to be optimal for the given kinase. The catalytic activity of tyrosine kinases is easured using the aftorementioned ELISA, whereas serine/threonine kinases are assayed using radioactive enzyme assays.
細胞アッセイ 細胞株 Human T blasts cell
濃度 0-4000 nM
反応時間 4 days
実験の流れ

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 10mg/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 this compound 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. This compound is added to freshly plated cells and cultured for 4 days. 3Hthymidine is added during the last 18 hours of the culture period.
動物実験 動物モデル DBA/2 and C57/BL6 mice
投薬量 0-136 ng/mL
投与方法 Administered via osmotic minipump infusion

参考

  • https://pubmed.ncbi.nlm.nih.gov/14593182/
  • https://pubmed.ncbi.nlm.nih.gov/14678034/
  • https://pubmed.ncbi.nlm.nih.gov/18242596/
  • https://pubmed.ncbi.nlm.nih.gov/22252297/
  • https://pubmed.ncbi.nlm.nih.gov/16378072/
  • https://pubmed.ncbi.nlm.nih.gov/14678034/

カスタマーフィードバック

Data from [Data independently produced by Arthritis Rheumatol , 2014, 66(1), 121-9]

Data from [Data independently produced by PLoS One, 2014, 9(11), e112014]

Data from [Data independently produced by Cancer Discov, 2012, 2(7), 591-7]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8] PubMed: 40147445
In silico modeling guides identification of novel JAK1 variants associated with immune dysregulation [ EMBO Mol Med, 2025, 10.1038/s44321-025-00317-0] PubMed: 41136770
Differential effects of tofacitinib on macrophage activation contribute to lack of response in ulcerative colitis patients [ J Crohns Colitis, 2025, 19(6)jjaf076] PubMed: 40320713
Keloids and inflammation: the crucial role of IL-33 in epidermal changes [ Front Immunol, 2025, 16:1514618] PubMed: 40230853
Rheumatoid arthritis associated cytokines and therapeutics modulate immune checkpoint receptor expression on T cells [ Front Immunol, 2025, 16:1534462] PubMed: 39981237
Polarization of Vδ2 T cells to a Th2-like phenotype promotes plasmablast differentiation and possesses pro-fibrotic properties in IgG4-related disease [ Front Immunol, 2025, 16:1550405] PubMed: 40213561
Membrane-bound IL-15 co-expression powers a potent and persistent CD70-targeted TRuC T-cell therapy [ Front Immunol, 2025, 16:1609658] PubMed: 40519930
Associations between ionomic profile and metabolic abnormalities in a murine model of sodium sulfide induced alopecia areata [ Front Pharmacol, 2025, 16:1507348] PubMed: 40438604
Targeting interferon responses in juvenile dermatomyositis: Siglec-1 as an in vitro biomarker for JAK inhibitor efficacy [ Rheumatology (Oxford), 2025, keaf227] PubMed: 40372702
Unidirectional Crosstalk Between NTRK1 and IGF2 Drives ER Stress in Chronic Pain [ Biomedicines, 2025, 13(7)1632] PubMed: 40722704

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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