Pamapimod

製品コードS8125 バッチS812501

印刷

化学情報

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）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	4.050mg/ml (9.97mM)	Taking the 1 mL working solution as an example, add 50 μL of 81 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.405mg/ml (1.00mM)	Taking the 1 mL working solution as an example, add 50 μL of 8.1 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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	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. This compound 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, this compound increased tolerance to pressure in a dose-dependent manner, suggesting an important role of p38 in pain associated with inflammation. It 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 this compound^[1].

プロトコル(参考用のみ)

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%. This compound was 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

参考

https://pubmed.ncbi.nlm.nih.gov/18776065/

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：

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。