Novel MK2 Inhibitors by Fragment Screening

Inhibitors of MAPKAP kinase 2 (MK2) are expected to attenuate the p38α signal transduction pathway in macrophages in a similar way to p38α inhibitors and to have a lower propensity for toxic side effects that have slowed the clinical development of the latter. Therefore, novel MK2 inhibitors may find therapeutic application in acute and chronic, TNFα-mediated inflammatory conditions like rheumatoid arthritis and others. Herein we have applied fragment screening, using physiologically relevant bioassays and fragment binding mode mapping by protein-observed NMR spectroscopy to the discovery of novel efficient chemical starting points for MK2