Literature DB >> 18945615

Pyrrolo-pyrimidones: a novel class of MK2 inhibitors with potent cellular activity.

Achim Schlapbach1, Roland Feifel, Stuart Hawtin, Richard Heng, Guido Koch, Henrik Moebitz, Laszlo Revesz, Clemens Scheufler, Juraj Velcicky, Rudolf Waelchli, Christine Huppertz.   

Abstract

Pyrrolo-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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Year:  2008        PMID： 18945615     DOI： 10.1016/j.bmcl.2008.10.039

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  14 in total

1.  Hit clustering can improve virtual fragment screening: CDK2 and PARP1 case studies.

Authors:  Alexey A Zeifman; Victor S Stroylov; Fedor N Novikov; Oleg V Stroganov; Alexandra L Zakharenko; Svetlana N Khodyreva; Olga I Lavrik; Ghermes G Chilov
Journal:  J Mol Model       Date:  2011-11-09       Impact factor: 1.810

Review 2.  Targeting innate immunity protein kinase signalling in inflammation.

Authors:  Matthias Gaestel; Alexey Kotlyarov; Michael Kracht
Journal:  Nat Rev Drug Discov       Date:  2009-06       Impact factor: 84.694

3.  Discovery of a Potent Dihydrooxadiazole Series of Non-ATP-Competitive MK2 (MAPKAPK2) Inhibitors.

Authors:  Jun Qin; Pawan Dhondi; Xianhai Huang; Robert Aslanian; James Fossetta; Fang Tian; Daniel Lundell; Anandan Palani
Journal:  ACS Med Chem Lett       Date:  2011-12-23       Impact factor: 4.345

4.  Modulating ADME Properties by Fluorination: MK2 Inhibitors with Improved Oral Exposure.

Authors:  Juraj Velcicky; Achim Schlapbach; Richard Heng; Laszlo Revesz; Daniel Pflieger; Ernst Blum; Stuart Hawtin; Christine Huppertz; Roland Feifel; Rene Hersperger
Journal:  ACS Med Chem Lett       Date:  2018-03-20       Impact factor: 4.345

Review 5.  Heat shock protein 27 phosphorylation: kinases, phosphatases, functions and pathology.

Authors:  Sergiy Kostenko; Ugo Moens
Journal:  Cell Mol Life Sci       Date:  2009-07-11       Impact factor: 9.261

6.  MAPK-activated protein kinase 2 contributes to Clostridium difficile-associated inflammation.

Authors:  Linda D Bobo; Rana E El Feghaly; Yee-Shiuan Chen; Erik R Dubberke; Zhuolin Han; Alexandra H Baker; Jinmei Li; Carey-Ann D Burnham; David B Haslam
Journal:  Infect Immun       Date:  2012-12-21       Impact factor: 3.441

Review 7.  Targeting Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts To Lead Small Molecule Inhibitors to Clinical Trials.

Authors:  Mario Fiore; Stefano Forli; Fabrizio Manetti
Journal:  J Med Chem       Date:  2015-11-09       Impact factor: 7.446

Review 8.  Regulation of cytokines by small RNAs during skin inflammation.

Authors:  Rasmus O Bak; Jacob G Mikkelsen
Journal:  J Biomed Sci       Date:  2010-07-01       Impact factor: 8.410

9.  Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement.

Authors:  C S Foster; A R Dodson; L Ambroisine; G Fisher; H Møller; J Clark; G Attard; J De-Bono; P Scardino; V E Reuter; C S Cooper; D M Berney; J Cuzick
Journal:  Br J Cancer       Date:  2009-08-25       Impact factor: 7.640

10.  Intravenous delivery of targeted liposomes to amyloid-β pathology in APP/PSEN1 transgenic mice.

Authors:  Eric A Tanifum; Indrani Dasgupta; Mayank Srivastava; Rohan C Bhavane; Li Sun; John Berridge; Hoda Pourgarzham; Rashmi Kamath; Gabriela Espinosa; Stephen C Cook; Jason L Eriksen; Ananth Annapragada
Journal:  PLoS One       Date:  2012-10-31       Impact factor: 3.240
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