Tofacitinib (CP-690550) Citrate

製品コードS5001 バッチS500111

印刷

化学情報

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

C16H20N6O.C6H8O7
分子量 504.49 CAS No. 540737-29-9
Solubility (25°C)* 体外 DMSO 100 mg/mL warmed with 50ºC water bath (198.21 mM)
Water Insoluble
Ethanol Insoluble
* <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 トファシチニブクエン酸塩 (Tofacitinib citrate (CP-690550、タソシチニブ)) は JAK の新規阻害剤です。IC50は JAK3, JAK2, JAK1 に対してそれぞれ 1 nM, 20 nM, 112 nM です。 トファシチニブクエン酸塩は抗感染作用を持ちます。
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). [2] Additionally, Tofacitinib citrate prevents IL-15-induced CD69 expression in human and cynomolgus monkey NK and CD8+ T cells in vitro. [3]
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.[2] 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.[3]

プロトコル(参考用のみ)

キナーゼアッセイ Enzyme assays
The JAK1, JAK2, and JAK3 kinase assays utilize a protein expressed in baculovirus-infected SF9 cells (a fusion protein of GST and the catalytic domain of human JAK enzyme) purified by affinity chromatography on glutathione−Sepharose. The substrate for the reaction is polyglutamic acid-tyrosine [PGT (4:1)], coated onto Nunc Maxi Sorp plates at 100 μg/mL overnight at 37 °C. The plates are washed three times, and JAK enzyme is added to the wells, which contained 100 μL of kinase buffer (50 mM HEPES, pH 7.3, 125 mM NaCl, 24 mM MgCl2) + ATP + 1 mM sodium orthovanadate). For Tofacitinib citrate, it is also added for kinase assay at different doses. After incubation at room temperature for 30 min, the plates are washed three times. The level of phosphorylated tyrosine in a given well is determined by standard ELISA assay utilizing an anti-phosphotyrosine antibody.
細胞アッセイ 細胞株 FDCP-EpoR JAK2WT and JAK2V617F cell lines
濃度 0-4 μM
反応時間 72 hours
実験の流れ

Determination of growth inhibition by Tofacitinib citrate is performed using identical culture conditions for both FDCP-EpoR JAK2WT and JAK2V617F cell lines. Briefly, 1 × 105 cells/mL are cultured in 96-well flat-bottom plates at 37 °C in a humidified 5% CO2 atmosphere using RPMI 1640 supplemented with 1.25% FCS, and 5% WEHI supernatant. Decreased FCS concentration is necessary to prevent binding between Tofacitinib citrate and serum proteins. Growth inhibition assays are terminated by addition of 20 μL CellTiter96 One Solution Reagent. Flat-bottom plates are incubated for an additional 3 hours for MTT assay. Absorbance is determined at 595 nm on a BioTek Synergy-HT microplate reader. Results are the average standard deviation of three independent determinations.
動物実験 動物モデル Mauritius-origin adult cynomolgus monkeys
投薬量 10, 30 mg/kg/d
投与方法 Oral gavage

カスタマーフィードバック

Data from [Biochem Biophy Res Commun, 2010, 402, 500–506]

, , Dr. Akihiko Yoshimura of Akihiko Yoshimura

Data independently produced by , , Saraswati Sukumar of Johns Hopkins University School of Medicine

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 panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection [ Antimicrob Agents Chemother, 2024, 68(4):e0135023.] PubMed: 38470034
Effect of JAK inhibitors on the three forms of bone damage in autoimmune arthritis: joint erosion, periarticular osteopenia, and systemic bone loss [ Inflamm Regen, 2023, 43(1):44] PubMed: 37726797
Comprehensive protocols for culturing and molecular biological analysis of IBD patient-derived colon epithelial organoids [ Front Immunol, 2023, 14:1097383] PubMed: 36911731
Comprehensive protocols for culturing and molecular biological analysis of IBD patient-derived colon epithelial organoids [ Front Immunol, 2023, 14:1097383] PubMed: 36911731
In vitro and in vivo modelling of mutant JAK3/STAT5 signaling in leukemia [ Heliyon, 2023, 9(11):e22085] PubMed: 38053908
Treatment of rheumatoid arthritis with baricitinib or upadacitinib is associated with reduced scaffold protein NEDD9 levels in CD4+ T cells [ Physiol Rep, 2023, 11(19):e15829] PubMed: 37771106
Effect of JAK inhibitors on the three forms of bone damage in autoimmune arthritis: joint erosion, periarticular osteopenia, and systemic bone loss [ Inflamm Regen, 2023, 43(1):44] PubMed: 37726797
Treatment of rheumatoid arthritis with baricitinib or upadacitinib is associated with reduced scaffold protein NEDD9 levels in CD4+ T cells [ Physiol Rep, 2023, 11(19):e15829] PubMed: 37771106
CD45-targeted antibody-drug-conjugate successfully conditions for allogeneic hematopoietic stem cell transplantation [ Blood, 2022, blood.2021012366] PubMed: 34986233
Lymphocyte crosstalk is required for monocyte-intrinsic trained immunity to Plasmodium falciparum [ J Clin Invest, 2022, 132(11)e139298] PubMed: 35642634

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。