Novel MK2 Inhibitors by Fragment Screening

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

Journal Name: Combinatorial Chemistry & High Throughput Screening

Volume 12 , Issue 7 , 2009

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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

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

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Article Details

VOLUME: 12
ISSUE: 7
Year: 2009
Page: [697 - 703]
Pages: 7
DOI: 10.2174/138620709788923700
Price: $58

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