Ruxolitinib Phosphate

製品コードS5243 バッチS524304

印刷

化学情報

Chemical Structure Synonyms INCB018424, INC424 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C17H18N6.H3O4P
分子量 404.36 CAS No. 1092939-17-7
Solubility (25°C)* 体外 DMSO 81 mg/mL (200.31 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 Ruxolitinib Phosphate (INCB018424, INC424) is the phosphate salt form of Ruxolitinib. Ruxolitinib is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3. Ruxolitinib kills tumor cells through toxic mitophagy. Ruxolitinib induces autophagy and enhances apoptosis.
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 h
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 o.g.

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：

N6-methyladenosine modification positively regulate Japanese encephalitis virus replication [ Virol J, 2024, 21(1):23] PubMed: 38243270
HDAC Inhibition Restores Response to HER2-Targeted Therapy in Breast Cancer via PHLDA1 Induction [ Int J Mol Sci, 2023, 24(7)6228] PubMed: 37047202
Paradoxical activation of chronic lymphocytic leukemia cells by ruxolitinib in vitro and in vivo [ Front Oncol, 2023, 13:1043694] PubMed: 37114129
IL-13 neutralization attenuates carotid artery intimal hyperplasia and increases endothelial cell migration via modulating the JAK-1/STAT-3 signaling pathway [ Cell Adh Migr, 2023, 17(1):1-10] PubMed: 37814455
RECOVER identifies synergistic drug combinations in vitro through sequential model optimization [ Cell Rep Methods, 2023, 3(10):100599] PubMed: 37797618
MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [ Cancer Cell, 2022, S1535-6108(21)00662-0] PubMed: 35051357
SLAMF7 engagement superactivates macrophages in acute and chronic inflammation [ Sci Immunol, 2022, 7(68):eabf2846] PubMed: 35148199
CD45-targeted antibody-drug-conjugate successfully conditions for allogeneic hematopoietic stem cell transplantation [ Blood, 2022, blood.2021012366] PubMed: 34986233
Ebola virus VP35 hijacks the PKA-CREB1 pathway for replication and pathogenesis by AKIP1 association [ Nat Commun, 2022, 13(1):2256] PubMed: 35474062
Pyruvate Facilitates FACT-Mediated γH2AX Loading to Chromatin and Promotes the Radiation Resistance of Glioblastoma [ Adv Sci (Weinh), 2022, 10.1002/advs.202104055] PubMed: 35048565

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。