p38α mitogen-activated protein kinase (MAPK) is activated in cancer cells in response to environmental factors, oncogenic stress, radiation, and chemotherapy. p38α MAPK phosphorylates a number of substrates, including MAPKAP-K2 (MK2), and regulates the production of cytokines in the tumor microenvironment, such as TNF-α, interleukin-1β (IL-1β), IL-6, and CXCL8 (IL-8)[3]. LY2228820 is a novel and effective p38α MAPK inhibitor with an IC50 value of 7 nM in cell free assay. To assess p38α activity in cells more directly, RAW 264.7 cells were treated with LY2228820. It inhibited p38α and the level of pMK2 (phospho-MAPKAP-K2) with IC50s of 7 nM and 34.3 nM, respectively. LY2228820 was orally dosed in Balb/c mice followed by iv LPS administration after 2 h. And the threshold minimum 50% effective dose (TMED50) was less than 1 mg/kg. In the rat CIA (collagen induced arthritis) model, LY2228820 effectively acting on foot swelling, bone erosion, and cartilage destruction, with the TMED50 of 1.5 mg/kg[4].
Ralimetinib dimesylate 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
A-2780
1 μM
Function assay
reduces tumor-driven cord formation
23335506
A549
~20 μM
Function assay
inhibits LPS-induced CXCL8 production with IC50 of 144.9 nM
24356814
CD14+
~800 nM
Function assay
inhibits osteoclastogenesis from CD14 positive cells
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