Novel MK2 Inhibitors by Fragment Screening

Title: Novel MK2 Inhibitors by Fragment Screening

Volume: 12 Issue: 7

Author(s): Oliver Keminer, Joachim Kraemer, Jan Kahmann, Ina Sternberger, Christoph Scheich, Joern Jungmann, Sabine Schaertl, Dirk Winkler, Osamu Ichihara, Mark Whittaker, Dirk Ullmann and Thomas Hesterkamp

Affiliation:

Keywords: MAPKAP kinase, p38α, MK2, fragment, TNFα, TROSY

Abstract: 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

Cite this article as:

Keminer Oliver, Kraemer Joachim, Kahmann Jan, Sternberger Ina, Scheich Christoph, Jungmann Joern, Schaertl Sabine, Winkler Dirk, Ichihara Osamu, Whittaker Mark, Ullmann Dirk and Hesterkamp Thomas, Novel MK2 Inhibitors by Fragment Screening, Combinatorial Chemistry & High Throughput Screening 2009; 12 (7) . https://dx.doi.org/10.2174/138620709788923700