LY2228820，又称Ralimetinibdimesylate，是一种高效的、选择性、ATP竞争抑制剂，作用于p38 MAPK的α和β亚型，IC50分别为5.3 nM和3.2 nM。在anisomycin刺激的HeLa细胞中，LY2228820有效抑制MK2（Thr334）磷酸化。在多发性骨髓瘤（MM）细胞中，LY2228820抑制破骨细胞生成（osteoclastogenesis），通过抑制p38 MAPK下游靶标HSP27磷酸化，从而显著阻断p38 MAPK信号通路，该作用并不会影响HSP27蛋白表达水平，而且LY2228820提高bortezomib诱导的细胞毒性和细胞凋亡。另外，LY2228820抑制IL-6和MIP-1α分泌。在A549 NSCLC移植瘤模型中，LY2228820引起显著的肿瘤生长延迟。

参考文献

[1] Mader M, et al. Imidazolylbenzimidazoles and imidazo[4,5-b]pyridines as potent p38alpha MAP kinase inhibitors with excellent in vivo antiinflammatory properties. Bioorg Med ChemLett, 18(1): 179-183 (2008).

[2] Ishitsuka K, et al. p38 mitogen-activated protein kinase inhibitor LY2228820 enhances bortezomib-induced cytotoxicity and inhibits osteoclastogenesis in multiple myeloma; therapeutic implications. Br J Haematol, 141(5): 598-606 (2008).

[3] Tate CM, et al. LY2228820 Dimesylate, a Selective Inhibitor of p38 Mitogen-activated Protein Kinase, Reduces Angiogenic Endothelial Cord Formation in Vitro and in Vivo. The Journal of Biological Chemistry288: 6743-6753 (2013).

[4] Campbell RM, et al.Characterization of LY2228820 dimesylate, a potent and selective inhibitor of p38 MAPK with antitumor activity. Mol Cancer Ther. 13(2):364-374 (2014).

冰袋运输。粉末直接保存于-20 ºC，有效期2年。溶于DMSO。建议分装后-20ºC避光保存，避免反复冻存，至少可存放6个月。