Front Cover: An Angle on MK2 Inhibition—Optimization and Evaluation of Prevention of Activation Inhibitors (ChemMedChem 19/2019)

Abstract

The Front Cover shows pillars of drug discovery projects and key questions to ask to avoid getting “lost in translation”. Each project needs a) a hypothesis that modulating protein X could benefit disease Y, b) a design strategy to make leads modulating protein X, and c) a translational screening cascade linking the target and hypothesis. Following structure–activity through the cascade is critical to validate or challenge the project hypothesis. In this case, potent p38 inhibitors were designed to show differential activity on kinases MK2 and MSK1, but this did not translate into preservation of pro‐resolution IL‐10 while inhibiting pro‐inflammatory TNF‐α, contrary to the project hypothesis. More information can be found in the Full Paper by Katerina Pardali, Mickael Mogemark et al. on page 1701 in Issue 19, 2019 (DOI: 10.1002/cmdc.201900303).