LY2228820 is a potent and selective ATP-competitive inhibitor of the α- and β-isoforms of p38 mitogen-activated protein kinases (MAPKs). It inhibits p38α and p38β with IC50 values of 5.3 nM and 3.2 nM, respectively. [1] In cell-based assays, LY2228820 selectively inhibited the level of phospho-MAPKAP-K2 (pMK2) in anisomycin-induced RAW264.7 cells, with IC50 of 35.3 nM. LY2228820 also inhibits lipopolysaccharide (LPS)/IFN-γ-induced TNFα formation in murine peritoneal macrophages, with IC50 of 6.3 nM. [1] Furthermore, LY2228820 inhibits angiogenic endothelial cord formation in multiple in vitro and in vivo assay models. [2]
LY2228820 is currently being evaluated in Phase I/II clinical trials in patients with newly diagnosed glioblastoma [3] and platinum-sensitive ovarian cancer [4]."