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p38 MAP Kinase Inhibitor Ralimetinib, LY2228820 Dimesylate Barrantes IDB and Nebreda AR1; Tate CM, et al2; Alspach E, et al3; Schultz RM 4 Drug Discovery Platform: Cancer Cell Signaling p38 MAP Kinase Inhibitor Ralimetinib, LY2228820 Dimesylate Target Molecule p38 mitogen-activated protein (MAP) kinase is activated in response to inflammatory stimuli (eg, tumor necrosis factor, interleukin-6), growth factors (eg, vascular endothelial growth factor, fibroblast growth factor, insulin-like growth factor), and cellular stress (eg, chemotherapeutic challenge). These conditions are prevalent in the initiation and progression of tumor growth and during the development of metastases. In addition to promoting cancer cell survival and growth, p38 also enhances invasion, angiogenesis, and metastasis.1-4 Ralimetinib (LY2228820 dimesylate) is a small molecule that in vitro preferentially binds to and inhibits p38 MAP kinase.5,6 Clinical Development Ralimetinib is being investigated in a clinical trial in patients with ovarian cancer. Study Schemas Not Available [NCT01663857] Genitourinary Cancer A Study of LY2228820 for Recurrent Ovarian Cancer The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated. References: 1. Barrantes IDB, Nebreda AR. Biochem Soc Trans. 2012;40(1):79-84. 2. Tate CM, et al. J Biol Chem. 2013;288(9):6743-6753. 3. Alspach E, et al. Cancer Discov. 2014;4(6):716-729. 4. Schultz RM. Prog Drug Res. 2013;60:59-92. 5. Ishitsuka K, et al. Br J Haematol. 2008;141(5):598-606. 6. Campbell RM, et al. Mol Cancer Ther. 2014;13(2):364-374. ON99508 02/2017 PRINTED IN USA © Lilly USA, LLC 2017. All rights reserved.