受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C19H9Cl2F2N3OS |
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分子量 | 436.26 | CAS No. | 209410-46-8 | ||||
Solubility (25°C)* | 体外 | DMSO | 87 mg/mL (199.42 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 | Neflamapimod (VX-745) is a potent and selective inhibitor of p38α with IC50 of 10 nM, 22-fold greater selectivity versus p38β and no inhibition to p38γ. |
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in vitro | VX-745 selectively inhibits p38α and p38β MAPK with IC50 of 10 nM and 220 nM, respectively, but not p38γ MAPK and a large panel of other kinases, with IC50 larger than 20 µM. In a human peripheral blood mononuclear cell (PBMC) assay, VX-745 provides IC50 of 56 and 52 nM for IL-1β and TNFα, respectively. VX-745 blocks IL-6 and IL-8 production induced by IL-1 and TNFα, and COX-2 synthesis mediated by LPS and IL-1β. [1-3] VX-745 (60 nM-20 µM) inhibits IL-6 and VEGF secretion in bone marrow stromal cells (BMSCs), without affecting their viability. VX-745 also inhibits TNF-α-induced IL-6 secretion in BMSCs. VX-745 inhibits both multiple myeloma (MM) cell proliferation and IL-6 secretion in BMSCs triggered by adherence of MM cells to BMSCs, suggesting that VX-745 can inhibit paracrine multiple myeloma (MM) cell growth in the BM milieu and overcome cell adhesion-related drug resistance. [4] |
in vivo | VX-745 is effective against adjuvant-induced arthritis (AA) in the rat with ED50 of 5 mg/kg. Histological scores for VX-745 in AA rats are 93% inhibition of bone resorption and 56% inhibition of inflammation. In the classical cartilage-induced arthritis model, VX-745 exhibits a dose-responsive decrease in severity score. [1-3] In a type II collagen-induced arthritis (CIA) mice model, VX-745 (2.5, 5, and 10 mg/kg) has 27%, 31%, and 44% improvement in the inflammatory scores, respectively, when compared to vehicle-treated mice. In addition, histological scores show a 32-39% protection of bone and cartilage erosion by VX-745. [5] |
特徴 | A potent and selective inhibitor to p38α and p38β MAPK. |
キナーゼアッセイ | Spectrophotometric coupled-enzyme assay | |
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The IC50 for the inhibition of p38α and p38β homologs are obtained by a spectrophotometric coupled-enzyme assay. A fixed concentration of enzyme (15 nM of p38α or p38β) is incubated with VX-745 in DMSO for 10 min. at 30 °C in 0.1 M HEPES buffer, pH 7.5, containing 10% glycerol, 10 mM MgCl2, 2.5 mM phosphoenolpyruvate, 200 µM NADH, 150 µg/mL pyruvate kinase, 50 µg/mL lactate dehydrogenase, and 200 µM EGF receptor peptide (KRELVEPLTPSGEAPNQALLR). The reaction is initiated with 100 µM and 70 µM ATP for p38α and p38β assays, respectively. The decrease of absorbance at 340 nm is monitored to follow the rate of the reaction. IC50 is evaluated from the rate data as a function of the inhibitor concentration. | ||
細胞アッセイ | 細胞株 | Human bone marrow stromal cells (BMSCs) and multiple myeloma (MM) cells |
濃度 | 60 nM - 20 μM, dissolved in DMSO. | |
反応時間 | 48 hours | |
実験の流れ | BMSCs (5 × 104 cells/well) or MM cells (3 × 104 cells/well) are incubated in 96-well culture plates in the presence or absence of VX-745 for 48 hours at 37 °C. DNA synthesis is measured by [3H]-thymidine ([3H]TdR) uptake. Cells are pulsed with [3H]TdR (0.5 μCi/well [.0185 MBq]) during the last 8 hours of 48-hour cultures. Growth inhibition of both MM cells and BMSCs by VX-745 is also assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) dye absorbance. | |
動物実験 | 動物モデル | Type II collagen-induced arthritis (CIA) mice model (DBA/1J) |
投薬量 | 2.5, 5, and 10 mg/kg | |
投与方法 | Oral gavage twice daily |
Data from [Data independently produced by , , FASEB J, 2018, doi:10.1096/fj.201801977R]
Konjac Ceramide (kCer)-Mediated Signal Transduction of the Sema3A Pathway Promotes HaCaT Keratinocyte Differentiation [ Biology (Basel), 2022, 11(1)121] | PubMed: 35053118 |
TPL-2 kinase induces phagosome acidification to promote macrophage killing of bacteria [ EMBO J, 2021, e106188] | PubMed: 33881780 |
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19] | PubMed: 32645325 |
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19] | PubMed: 32645325 |
Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling [ Dev Cell, 2020, S1534-5807(20)30757-7] | PubMed: 33080171 |
p38 MAPK signalling regulates cytokine production in IL-33 stimulated Type 2 Innate Lymphoid cells. [ Sci Rep, 2020, 10(1):3479] | PubMed: 32103032 |
IL-33 regulates cytokine production and neutrophil recruitment via the p38 MAPK-activated kinases MK2/3 [ Immunol Cell Biol, 2019, 97(1):54-71] | PubMed: 30171775 |
Clinically Advanced p38 Inhibitors Suppress DUX4 Expression in Cellular and Animal Models of Facioscapulohumeral Muscular Dystrophy. [ J Pharmacol Exp Ther, 2019, 370(2):219-230] | PubMed: 31189728 |
Activating β-catenin/Pax6 axis negatively regulates osteoclastogenesis by selectively inhibiting phosphorylation of p38/MAPK [Jie Z FASEB J, 2018, 10.1096/fj.201801977R] | PubMed: 30526042 |
Differential control of Toll-like receptor 4-induced interleukin-10 induction in macrophages and B cells reveals a role for p90 ribosomal S6 kinases. [ J Biol Chem, 2018, 293(7):2302-2317] | PubMed: 29229781 |
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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