ly3007113

LY3007113 is an orally active small molecule inhibitor of p38 mitogen-activated protein kinase (MAPK), specifically targeting the p38α isoform. It was developed by Eli Lilly for its potential immunomodulating, anti-inflammatory, and antineoplastic activities. By inhibiting p38 MAPK-mediated signaling, LY3007113 suppresses the production of proinflammatory cytokines such as TNF-α and interleukins (IL-1, IL-6) and can induce apoptosis in tumor cells. Preclinical studies demonstrated activity in various cancer models including HeLa cells, glioblastoma xenografts (U87MG), ovarian cancer, kidney cancer, and leukemia. In clinical trials for advanced cancers, the drug showed dose-proportional pharmacokinetics but did not achieve a biologically effective dose due to toxicity concerns. Development was discontinued after phase 1 trials because sustained target inhibition could not be achieved at tolerable doses[1][2][3][4][5][7].