LY2228820是一种新型有效的p38 MAPK抑制剂，无细胞试验中IC50为7 nM，不改变p38 MAPK的活化。

＞98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

Ralimetinib dimesylate; LY2228820 dimesylate; LY2228820 2MsOH; LY 2228820; LY-2228820

powder

Water ：92 mg/mL warmed (150.1 mM)

DMSO ：4 mg/mL warmed (6.52 mM)

Ethanol ：3 mg/mL (4.89 mM)

p38α

LY2228820 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, LY2228820 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, 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. LY2228820 (200 nM–400 nM) enhances bortezomib-induced cytotoxicity and apoptosis, but LY2228820 alone doesn’t inhibit the growth of MM.1S cells. LY2228820 (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. LY2228820 (400 nM–800 nM) also blocks osteoclastogenesis from CD14+ cells.

In LPS-induced mice, LY2228820 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), LY2228820 displays potent effects on paw swelling, bone erosion, and cartilage destruction, with a threshold minimum 50% effective dose (TMED50)of 1.5 mg/kg.

[1] Mader M, et al. Bioorg Med Chem Lett, 2008, 18(1), 179-183.

[2] Ishitsuka K, et al. Br J Haematol, 2008, 141(5), 598-606.

[3] Ishitsuka K, et al. Oncogene, 2005, 24(38), 5888-5896.