S-Ruxolitinib (INCB018424)

製品コードS2902 バッチS290202

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C17H18N6
分子量 306.37 CAS No. 941685-37-6
Solubility (25°C)* 体外 DMSO 61 mg/mL (199.1 mM)
Ethanol 61 mg/mL (199.1 mM)
Water 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.
* <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 S-Ruxolitinib は INCB018424 のキラル体であり、これは JAK1/2 阻害剤として初めて臨床応用された強力かつ選択的な阻害剤で、IC50 は 3.3 nM/2.8 nM、JAK1/2 に対する JAK3 との選択性は 130 倍以上です。現在第 3 相臨床試験中です。
in vitro S-Ruxolitinib (INCB018424) potently and selectively inhibits JAK2V617F-mediated signaling and proliferation in Ba/F3 cells and HEL cells. It markedly increases apoptosis in a dose dependent manner in Ba/F3 cells. This compound (64 nM) results in a doubling of cells with depolarized mitochondria in Ba/F3 cells. It inhibits proliferating of erythroid progenitors from normal donors and polycythemia vera patients with IC50 of 407 nM and 223 nM, respectively. INCB018424 demonstrates remarkable potency against erythroid colony formation with IC50 of 67nM.
in vivo S2902 (180 mg/kg, orally, twice a day) results in survive rate of greater than 90% by day 22 in a JAK2V617F-driven mouse model. S2902(180 mg/kg, orally, twice a day) markedly reduces splenomegaly and circulating levels of inflammatory cytokines, and preferentially eliminated neoplastic cells, resulting in significantly prolonged survival without myelosuppressive or immunosuppressive effects in a JAK2V617F-driven mouse model. The primary end point is reached in 41.9% of patients in the S2902 group as compared with 0.7% in the placebo group in the double-blind trial of myelofibrosis. Ruxolitinib results in maintaining of reduction in spleen volume and improvement of 50% or more in the total symptom score. A total of 28% of the patients in the S2902 (15 mg twice daily) group has at least a 35% reduction in spleen volume at week 48 in patients with myelofibrosis, as compared with 0% in the group receiving the best available therapy. The mean palpable spleen length has decreased by 56% with S2902 but has increased by 4% with the best available therapy at week 48. Patients in the S2902 group has an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis.

プロトコル(参考用のみ)

キナーゼアッセイ Binding assay
Recombinant proteins are expressed using Sf21 cells and baculovirus vectors and purified with affinity chromatography. JAK kinase assays use a homogeneous time-resolved fluorescence assay with the peptide substrate (-EQEDEPEGDYFEWLE). Each enzyme reaction is carried out with S-Ruxolitinib (INCB018424) or control, JAK enzyme, 500 nM peptide, adenosine triphosphate (ATP; 1mM), and 2% dimethyl sulfoxide (DMSO) for 1 hour. The 50% inhibitory concentration (IC50) is calculated as the concentration of this compound required for inhibition of 50% of the fluorescent signal.
細胞アッセイ 細胞株 Ba/F3 and HEL cells
濃度 3 μM
反応時間 48 hours
実験の流れ Cells are seeded at 2 × 103/well of white bottom 96-well plates and treated with S-Ruxolitinib (INCB018424) from DMSO stocks (0.2% final DMSO concentration), followed by incubation for 48 hours at 37 ℃ with 5% CO2. Viability is measured by cellular ATP determination using the Cell-Titer Glo luciferase reagent or viable cell counting. Values are transformed to percent inhibition relative to vehicle control, and IC50 curves are fitted according to nonlinear regression analysis of the data using PRISM GraphPad.
動物実験 動物モデル JAK2V617F-driven mouse model
投薬量 180 mg/kg
投与方法 Oral gavage

参考

  • https://pubmed.ncbi.nlm.nih.gov/20130243/
  • https://pubmed.ncbi.nlm.nih.gov/22375971/
  • https://pubmed.ncbi.nlm.nih.gov/22375970/

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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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