Pyrrolo-pyrimidones: A novel class of MK2 inhibitors with potent cellular activity
2008; Elsevier BV; Volume: 18; Issue: 23 Linguagem: Inglês
10.1016/j.bmcl.2008.10.039
ISSN1464-3405
AutoresAchim Schlapbach, Roland Feifel, Stuart Hawtin, Richard Heng, Guido Koch, Henrik Moebitz, Láśzló Révész, Clemens Scheufler, Juraj Velcicky, Rudolf Waelchli, Christine Huppertz,
Tópico(s)Cancer Mechanisms and Therapy
ResumoPyrrolo-pyrimidones of the general structure 1 were synthesized and evaluated for their potential as MK2 inhibitors. Potent derivatives were discovered which inhibit MK2 in the nanomolar range and show potent inhibition of cytokine release from LPS-stimulated monocytes. These derivatives were shown to inhibit phosphorylation of hsp27, a downstream target of MK2 and are modestly selective in a panel of 28 kinases.
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