受注:045-509-1970 |
技術サポート:[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
Synonyms | R-1503,Ro4402257 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
||||||||
化学式 | C19H20F2N4O4 |
||||||||||
分子量 | 406.38 | CAS No. | 449811-01-2 | ||||||||
Solubility (25°C)* | 体外 | DMSO | 81 mg/mL (199.32 mM) | ||||||||
Ethanol | 28 mg/mL (68.9 mM) | ||||||||||
Water | Insoluble | ||||||||||
体内 (毎回新しく調製した物を用意してください) |
|
||||||||||
* <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 | Pamapimod (R-1503, Ro4402257) is a novel, selective inhibitor of p38 mitogen-activated protein kinase. It inhibits p38α and p38β enzymatic activity with IC50 values of 0.014±0.002 and 0.48± 0.04 microM, respectively with no activity against p38delta or p38gamma isoforms. |
---|---|
in vitro | Pamapimod inhibited p38, but inhibition of JNK was not detected. Pamapimod also inhibited lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) α production by monocytes, interleukin (IL)-1β production in human whole blood, and spontaneous TNFα production by synovial explants from RA patients[1]. |
in vivo | In murine collagen-induced arthritis, pamapimod reduced clinical signs of inflammation and bone loss at 50 mg/kg or greater. In a rat model of hyperalgesia, pamapimod increased tolerance to pressure in a dose-dependent manner, suggesting an important role of p38 in pain associated with inflammation. Pamapimod suppresses spontaneous production of TNFα by synovial explants from RA patients. LPS- and TNFα-stimulated production of TNFα and IL-6 in rodents also was inhibited by pamapimod[1]. |
細胞アッセイ | 細胞株 | Human Monocytic Cell Line, THP-1 |
---|---|---|
濃度 | 15 μM | |
反応時間 | 150 min | |
実験の流れ | THP-1 cells, growing in log phase, were collected by centrifugation and resuspended in RPMI 1640 containing 5.5×10-5 M 2-mercaptoethanol and 10% fetal bovine serum to a final cell concentration of 2.5×106 cells/ml. Dilutions of pamapimod were predispensed in 25 μl aliquots (before addition of cells) into round-bottom 96-well plates. The starting concentration was 100 μM in 5% dimethyl sulfoxide, and six half-log serial dilutions were made. After the addition of 200 μl of cell suspension and 25 μl of 5 μg/ml LPS in medium, the final dimethyl sulfoxide concentration was 0.5%. Compounds were diluted an additional 10-fold, and the final LPS concentration was 500 ng/ml. The cell suspensions and compound dilutions were combined and incubated for 30 min at 37°C in a 5% CO2 humidified atmosphere, before the addition of LPS (or medium for non-LPS control samples). After the addition of LPS, plates were incubated for 2 h, followed by centrifugation to pellet cells. Cell supernatants were stored at 4°C until analysis for TNF-α content. TNF-α levels were determined by ELISA. Cytokine concentrations were determined. |
|
動物実験 | 動物モデル | BALB/c mice |
投薬量 | 25, 50, 100, 150 mg/kg | |
投与方法 | oral administration |
IL-33 promotes type 1 cytokine expression via p38 MAPK in human NK cells. [ J Leukoc Biol, 2020, 10.1002/JLB.3A0120-379RR] | PubMed: 32017227 |
p38α Regulates Expression of DUX4 in a Model of Facioscapulohumeral Muscular Dystrophy [ J Pharmacol Exp Ther, 2020, 374(3):489-498] | PubMed: 32576599 |
Corticosteroids inhibit Mycobacterium tuberculosis-induced necrotic host cell death by abrogating mitochondrial membrane permeability transition. [ Nat Commun, 2019, 10(1):688] | PubMed: 30737374 |
The Novel p38 Inhibitor, Pamapimod, Inhibits Osteoclastogenesis and Counteracts Estrogen-Dependent Bone Loss in Mice [ J Bone Miner Res, 2019, 34(5):911-922] | PubMed: 30615802 |
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 |
EGFR signaling suppresses type 1 cytokine-induced T-cell attracting chemokine secretion in head and neck cancer [ PLoS One, 2018, 13(9):e0203402] | PubMed: 30192802 |
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。