Pamapimod (R-1503, Ro4402257)是一种新型的、选择性的p38 MAPK抑制剂，Pamapimod能抑制p38α和p38β， IC50分别为0.014±0.002和0.48± 0.04 μM。
别名：R-1503, Ro4402257
Pamapimod (R-1503, Ro4402257)是一种新型的、选择性的p38 MAPK抑制剂，Pamapimod能抑制p38α和p38β， IC50分别为0.014±0.002和0.48± 0.04 μM。Pamapimod也能抑制LPS刺激下单核细胞TNFα的产生、人全血细胞中IL-1β的生成以及RA患者滑膜外植体的自发性TNFα的产生。
在体内研究中，Pamapimod（50 mg/kg）在小鼠胶原诱导性关节炎中能减少炎症临床症状以及减少骨质流失。在痛觉过敏的大鼠模型中，pamapimod能增强其耐压力，说明p38在炎症相关的疼痛中的重要作用。Pamapimod能抑制RA患者滑膜外植体的自发性TNFα的产生。在啮齿类动物中，pamapimod抑制LPS-和TNFα-刺激下TNFα和IL-6的生成。
| 体外实验* | |
|---|---|
| 细胞系 | Human Monocytic Cell Line, THP-1 |
| 方法 | 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. |
| 浓度 | 15 μM |
| 处理时间 | 150 min |
*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
| 体内实验* | |
|---|---|
| 动物模型 | BALB/c mice |
| 配制 | 0.9% NaCl, 0.5% sodium carboxymethylcellulose, 0.4% polysorbate 80, 0.9% benzyl alcohol, and 97.3% distilled water. |
| 剂量 | 25, 50, 100, 150 mg/kg |
| 给药处理 | oral administration |
*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
| 分子量 | 406.38 |
| 分子式 | C19H20F2N4O4 |
| CAS号 | 449811-01-2 |
| 溶解性（25°C） | DMSO 80 mg/mL Ethanol 20 mg/mL |
| 储存条件 |
粉末型式 -20°C 3年；4°C 2年 溶于溶剂 -80°C 6个月；-20°C 1个月 |
| 运输方式 | 冰袋运输，根据产品的不同，可能会有相应调整。 |
*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 2.4608 mL | 12.3038 mL | 24.6075 mL |
| 5 mM | 0.4922 mL | 2.4608 mL | 4.9215 mL |
| 10 mM | 0.2461 mL | 1.2304 mL | 2.4608 mL |
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 | |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km 系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
| 其他相关的p38 MAPK产品 |
|---|
| HWY336
HWY336 is a selective, non-ATP competitive dual MKK4 and MKK7 inhibitor with IC50 values of 6 µM on MKK4 and 10 µM on MKK7 in vitro. HWY336 inhibits the phosphorylation of MKK4/MKK7 inside the activation loop or hinders the substrate to access the kinase. |
| BSJ-04-122
BSJ-04-122 是一种共价 MKK4/7 双重抑制剂。BSJ-04-122 抑制 MKK4 和 MKK7，IC50 值分别为 4 nM 和 181 nM。 |
| OVA-E1 peptide TFA
OVA-E1 peptide TFA 是SIINFEKL [OVA (257-264)拮抗突变体。 |
| MBP MAPK Substrate
MBP MAPK Substrate 可以用作 MAPK 的外源底物。 |
| OVA-E1 peptide
OVA-E1 peptide 是SIINFEKL [OVA (257-264)拮抗突变体。 |
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