| 產(chǎn)品描述： | PF-3644022 is a potent, selective, orally active and ATP-competitive MAPKAPK2 (MK2) inhibitor with an IC50 of 5.2 nM and a Ki of 3 nM. PF-3644022 also inhibits MK3 and p38 regulated/activated kinase (PRAK) with IC50s of 53 nM and 5.0 nM, respectively. PF-3644022 potently inhibits TNFα production and has anti-inflammatory effect |
| 靶點(diǎn)： |
IC50: 5.2 nM (MK2), 5.0 nM (PRAK) and 53 nM (MK3).Ki: 3 nM (MK2);p38MAPK;?SerineProtease;?MAPK |
| 體外研究： |
The inhibitory activity of PF-3644022 against other MAPKAP kinase family members is evaluated. Other than MNK2 with an IC50 of 148 nM, other family members are largely not inhibited, showing at least several hundred-fold selectivity versus MK2.
In the human U937 monocytic cell line or peripheral blood mononuclear cells, PF-3644022 potently inhibits TNFα production with similar activity (IC50 of 160 nM). PF-3644022 blocks TNFα and IL-6 production in LPS-stimulated human whole blood with IC50 values of 1.6 and 10.3 μM, respectively. Inhibition of TNFα in U937 cells and blood correlates closely with inhibition of phospho-heat shock protein 27, a target biomarker of MK2 activity. |
| 體內(nèi)研究： |
PF-3644022 (3-100 mg/kg; oral gavage; twice a day; for 12 days; Lewis rats) treatment shows dose-dependent inhibition of chronic paw swelling measured on day 21 after 12 days of oral dosing, with ED50 value of 20 mg/kg. Animal Model: Female Lewis rats (125-140 g) injected with streptococcal cell wall Dosage: 3 mg/kg, 10 mg/kg, 30 mg/kg, 50 mg/kg, 100 mg/kg Administration: Oral gavage; twice a day; for 12 days Result: Showed dose-dependent inhibition of chronic paw swelling measured on day 21 after 12 days of oral dosing. |
| 參考文獻(xiàn)： |
1. Mourey RJ, et al. A benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. J Pharmacol Exp Ther. 2010 Jun;333(3):797-807. |
| 溶解性： |
Soluble in DMSO |
| 保存條件： |
-20℃ |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.671 ml |
13.353 ml |
26.705 ml |
| 5 mM |
0.534 ml |
2.671 ml |
5.341 ml |
| 10 mM |
0.267 ml |
1.335 ml |
2.671 ml |
| 50 mM |
0.053 ml |
0.267 ml |
0.534 ml |
|
| 注意： |
部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。 |
上海工商
危險(xiǎn)品化學(xué)品經(jīng)營許可證（不帶存儲(chǔ)）
營業(yè)執(zhí)照(三證合一)
北京