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Back Cover: Modular Assembly of Allosteric MEK Inhibitor Structural Elements Unravels Potency and Feedback‐Modulation Handles (ChemMedChem 12/2015)
Author(s) -
Hartung Ingo V.,
Pühler Florian,
Neuhaus Roland,
Scholz Arne,
Siemeister Gerhard,
Geisler Jens,
Hillig Roman C.,
von Ahsen Oliver,
Hitchcock Marion
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500530
Subject(s) - allosteric regulation , modular design , mek inhibitor , chemistry , potency , computational biology , kinase , cover (algebra) , protein kinase a , computer science , mapk/erk pathway , biochemistry , biology , in vitro , enzyme , engineering , mechanical engineering , operating system
The back cover picture shows our modular approach in reassembling previously described building blocks of inhibitors for the mitogen‐activated protein kinase kinase (MEK). We have combined our recently identified C6‐phenoxy side chains with cores derived from two MEK inhibitors that are currently in clinical development. This modular approach has allowed us to synthesize and characterize two novel series of highly potent allosteric MEK inhibitors. We report their pharmacokinetic properties and in vivo efficacy data for one advanced preclinical candidate. Inspection of effects of these new inhibitors on MEK phosphorylation allowed us to further unravel structural intricacies of MEK–Raf feedback interactions. More details can be found in the Full Paper by Ingo V. Hartung, Marion Hitchcock et al. on page 2004 in Issue 12, 2015 (DOI: 10.1002/cmdc.201500442).