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• 产品描述： Ralimetinib dimesylate (LY2228820 dimesylate) is a selective, ATP-competitive inhibitor of p38 MAPK α/β with IC50s of 5.3 and 3.2 nM, respectively. Ralimetinib (LY2228820) selectively inhibits phosphorylation of MK2 (Thr334), with no effect on phosphorylation of p38a MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc.

• 靶点： p38β MAPK：3.2 nM (IC50)；p38α MAPK：5.3 nM (IC50);Apoptosis; p38MAPK; Autophagy

• 体外研究：
  Ralimetinib dimesylate inhibits p38α, as well as the level of phosphoMAPKAPK-2 (pMK2) in RAW 264.7 cells, with IC50 values of 7 nM and 34.3 nM, respectively. Furthermore, Ralimetinib dimesylate inhibits lipopolysaccharide (LPS)-induced TNFα formation in murine peritoneal macrophages, with IC50 of 5.2 nM. In multiple myeloma (MM) cells, including INA6, RPMI-8226, U266, and RPMI-Dox40, Ralimetinib dimesylate (LY2228820) (200 nM-800 nM) significantly blocks p38MAPK signaling, as revealed by its inhibition on phosphorylation of HSP27, a downstream target of p38MAPK, without affecting the expression level of HSP27. Ralimetinib dimesylate (200 nM-400 nM) enhances bortezomib-induced cytotoxicity and apoptosis, but Ralimetinib dimesylate alone doesn't inhibit the growth of MM.1S cells. Ralimetinib dimesylate (200 nM-800 nM) also inhibits secretion of IL-6 and MIP-1α in long-term BM stromal cells (LT-BMSCs), BM mononuclear cells (BMMNCs), peripheral blood (PB) CD138+, CD138- or PB CD14+ cells. Ralimetinib dimesylate (400 nM-800 nM) also blocks osteoclastogenesis from CD14+ cells.

• 体内研究：
  In LPS-induced mice, Ralimetinib dimesylate effectively inhibits the formation of TNFα with a threshold minimum 50% effective dose (TMED50) less than 1 mg/kg. In a rat model of collagen-inducedarthritis (CIA), Ralimetinib dimesylate displays potent effects on paw swelling, bone erosion, and cartilage destruction, with a threshold minimum 50% effective dose (TMED50)of 1.5 mg/kg. Ralimetinib dimesylate inhibits tumor phospho-MK2 in a dose-dependent manner (TED50=1.95 mg/kg, TED70=11.17 mg/kg) in mice implanted with B16-F10 melanoma. Ralimetinib dimesylate inhibits MK2 phosphorylation: mouse in vivo TED50=1.01 mg/kg (compound exposure approximately 100 nM) and human ex vivo IC50=0.12 μM with either mouse or human PBMC.

• 参考文献：
  1. Mader M, et al. Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38alpha MAP kinase inhibitors with excellent in vivo antiinflammatory properties. Bioorg Med Chem Lett, 2008, 18(1), 179-183. 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, 2008, 141(5), 598-606. 3. Campbell RM, et al. Characterization of LY2228820 dimesylate, a potent and selective inhibitor of p38 MAPK with antitumor activity. Mol Cancer Ther. 2014 Feb;13(2):364-74.

• 溶解性： Soluble  in  DMSO、H2O

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	1.632 ml	8.16 ml	16.32 ml
  5 mM	0.326 ml	1.632 ml	3.264 ml
  10 mM	0.163 ml	0.816 ml	1.632 ml
  50 mM	0.033 ml	0.163 ml	0.326 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *