Momelotinib (CYT387)

製品コードS2219 バッチS221905

印刷

化学情報

Chemical Structure Synonyms LM-1149 , CYT11387 Storage
(From the date of receipt)		 3 years -20°C(in the dark) powder
化学式

C23H22N6O2
分子量 414.46 CAS No. 1056634-68-4
Solubility (25°C)* 体外 DMSO 83 mg/mL (200.26 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）
Clear solution
2%DMSO 40%PEG300 3%Tween80 55%ddH2O
2.0mg/ml Taking the 1 mL working solution as an example, add 20 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 30 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 550 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 Momelotinib (CYT387, LM-1149 , CYT11387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Momelotinib (CYT387) induces apoptosis and autophagy. Phase 3.
in vitro CYT387 inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC50 of 1400 nM. Furthermore, CYT387 also causes the inhibition of cell proliferation in cell lines constitutively activated by JAK2 or MPL signaling, including Ba/F3-MPLW515L cells, CHRF-288-11 cells and Ba/F3-TEL-JAK2 cells with IC50 of 200 nM, 1 nM and 700 nM, respectively. In addition, CYT387 has been shown to inhibit erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC50 of 2μ-4 μM. [1] A recent study shows that CYT387 inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, CYT387 induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies bortezomib and melphalan in primary multiple myeloma (MM) cells. [2]
in vivo In a murine MPN model, CYT387 normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines. [3]

プロトコル(参考用のみ)

キナーゼアッセイ Cell-free kinase activity assays
Glutathione-S-transferase (GST)-tagged JAK kinase domains expressed in insect cells are purified before use in a peptide substrate phosphorylation assay. Assays are carried out in 384-well optiplates using an Alphascreen Protein Tyrosine Kinase P100 detection kit and a PerkinElmer Fusion Alpha instrument.
細胞アッセイ 細胞株 Ba/F3, Ba/F3-JAK2V617F and Ba/F3-MPLW515L cells
濃度 0 to 10 μM
反応時間 72 hours
実験の流れ Ba/F3 cells expressing JAK2V617F (Ba/F3-JAK2V617F) and MPLW515L (Ba/F3-MPLW515L) mutants, as well as CHRF-288-11 (JAK2T875N) and CMK (JAK3A572V) cells are used. The TEL/JAK2 and TEL/JAK3 fusions are generated and introduced into Ba/F3 murine cells. The TEL/JAK2- or TEL/JAK3-transfected cells are cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal calf serum (FCS). Ba/F3 wild-type cells are cultured in RPMI containing 10% FCS supplemented with 5 ng/mL murine IL-3. Proliferation is measured using the Alamar Blue assay after incubating for 72 hours at 37 °C with 5% CO2
動物実験 動物モデル Balb/c mice are transplanted with bone marrow transduced with a JAK2V617F retrovirus.
投薬量 ≤50 mg/kg
投与方法 Administered via p.o.

カスタマーフィードバック

Data from [Data independently produced by J Clin Invest, 2014, 10.1172/JCI69094]

, 2014, Dr. Claude Haan and Catherine Rolvering from University of Luxembourg

Data from [Blood, 2012, 120(19), 4093-103]

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
AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophages [ Cell Rep, 2023, 42(9):113067] PubMed: 37659081
Systematic screening identifies ABCG2 as critical factor underlying synergy of kinase inhibitors with transcriptional CDK inhibitors [ Breast Cancer Res, 2023, 25(1):51] PubMed: 37147730
Surgical Reconstruction of Stage 3 and 4 Pressure Injuries: A Literature Review and Proposed Algorithm from an Interprofessional Working Group [ Adv Skin Wound Care, 2023, 36(5):249-258] PubMed: 37079788
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation [ Front Immunol, 2022, 13:1001068] PubMed: 36131914
Comprehensive drug response profiling and pan-omic analysis identified therapeutic candidates and prognostic biomarkers for Asian cholangiocarcinoma [ iScience, 2022, 25(10):105182] PubMed: 36248745
A Gene Co-Expression Network-Based Drug Repositioning Approach Identifies Candidates for Treatment of Hepatocellular Carcinoma [ Cancers (Basel), 2022, 14(6)1573] PubMed: 35326724
STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer [ Life Sci Alliance, 2022, 5(11)e202201460] PubMed: 35803738
Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis [ Cell Stem Cell, 2021, S1934-5909(21)00344-1] PubMed: 34529935

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。