Ruxolitinib

製品コードS1378 バッチS137816

印刷

化学情報

Chemical Structure Synonyms INCB018424 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. 941678-49-5
Solubility (25°C)* 体外 DMSO 61 mg/mL (199.1 mM)
Ethanol 31 mg/mL (101.18 mM)
Water 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 ルクソリチニブ (Ruxolitinib (INCB018424)) は、最初に臨床試験が行われた強力で選択的なJAK1/2 阻害剤であり、IC50 はそれぞれ 3.3 nM/ 2.8 nM、JAK1/2 に対して JAK3 の 130 倍の選択性を示します。ルクソリチニブはマイトファジー (mitophagy) によって抗腫瘍作用を示します。また、オートファジー (autophagy) を誘導し、アポトーシス (apoptosis) を促進します。
in vitro INCB018424 potently and selectively inhibits JAK2V617F-mediated signaling and proliferation in Ba/F3 cells and HEL cells. INCB018424 markedly increases apoptosis in a dose dependent manner in Ba/F3 cells. INCB018424 (64 nM) results in a doubling of cells with depolarized mitochondria in Ba/F3 cells. INCB018424 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. [1]
in vivo INCB018424 (180 mg/kg, orally, twice a day) results in survive rate of greater than 90% by day 22 in a JAK2V617F-driven mouse model. INCB018424 (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. [1] The primary end point is reached in 41.9% of patients in the Ruxolitinib 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. [2] A total of 28% of the patients in the Ruxolitinib (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 Ruxolitinib but has increased by 4% with the best available therapy at week 48. Patients in the ruxolitinib group has an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis. [3]

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 Ruxolitinib 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 INCB018424 concentration 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, treated with INCB018424 from DMSO stocks (0.2% final DMSO concentration), and incubated 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

カスタマーフィードバック

Data from [Data independently produced by Blood, 2014, 123(24), 3832-42]

Data from [Data independently produced by Gene Ther, 2014, 10.1038/gt.2014.83]

Data from [Data independently produced by J Immunol, 2012, 189(6), 2784-92]

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：

Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer [ Nat Commun, 2024, 15(1):2503] PubMed: 38509064
Inhibition of neutrophil swarming by type I interferon promotes intracellular bacterial evasion [ Nat Commun, 2024, 15(1):8663] PubMed: 39375351
Gadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms [ Nat Commun, 2024, 15(1):2989] PubMed: 38582902
Defective N-glycosylation of IL6 induces metastasis and tyrosine kinase inhibitor resistance in lung cancer [ Nat Commun, 2024, 15(1):7885] PubMed: 39251588
Neuroinflammatory disease signatures in SPG11-related hereditary spastic paraplegia patients [ Acta Neuropathol, 2024, 147(1):28] PubMed: 38305941
Tumor cell senescence-induced macrophage CD73 expression is a critical metabolic immune checkpoint in the aging tumor microenvironment [ Theranostics, 2024, 14(3):1224-1240] PubMed: 38323313
JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors [ J Exp Clin Cancer Res, 2024, 43(1):64] PubMed: 38424636
A novel strategy to generate immunocytokines with activity-on-demand using small molecule inhibitors [ EMBO Mol Med, 2024, 16(4):904-926] PubMed: 38448543
Somatic PDGFRB activating variants promote smooth muscle cell phenotype modulation in intracranial fusiform aneurysm [ J Biomed Sci, 2024, 31(1):51] PubMed: 38741091
Somatic PDGFRB activating variants promote smooth muscle cell phenotype modulation in intracranial fusiform aneurysm [ J Biomed Sci, 2024, 31(1):51] PubMed: 38741091

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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