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Synonyms | LM-1149 , CYT11387 | Storage (From the date of receipt) |
3 years -20°C(in the dark) powder | ||||
化学式 | C23H22N6O2 |
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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) |
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* <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. |
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. |
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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] |
キナーゼアッセイ | Cell-free kinase activity assays | |
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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. |
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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]
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 |
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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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