The 'retro-design' concept for novel kinase inhibitors.
Protein kinases are among the most attractive therapeutic targets for a broad range of diseases. This feature review highlights and classifies the main design principles employed to generate active and selective kinase inhibitors. In particular, emphasis is focused on a fragment-based lead-generation approach, which constitutes a novel design method for developing type II kinase inhibitors with distinct binding kinetic attributes. This 'retro-design' strategy relies on a customized fragment library, and contrasts the traditional approach used in the design of type II inhibitors.
Müller
Gerhard
G
Proteros Fragments GmbH, Fraunhoferstrasse 20, 82152 Martinsried, Germany. mueller@proteros-fragments.com
Sennhenn
Peter C
PC
Woodcock
Timothy
T
Neumann
Lars
L
D000818:Animals; D020134:Catalytic Domain; D017076:Computer-Aided Design; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods*
D019151:Peptide Library; D010455:Peptides; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases