Binding Modes for Early Kinase Inhibitors

Key hydrogen bonds are shown as dotted lines. Lapatinib (4.4) extends into an adjacent pocket by displacing the C-helix. 

3 Diverse Binding Modes for Recent Kinase Inhibitors 

So far, few inhibitors have been demonstrated to bind in the part of the catalytic site that is used by phosphoacceptor substrates. This is thought to reflect the geometry and physical properties of these sites often being unsuitable for lead-like small molecules. Accordingly, many of these compounds (compound 4.17) are peptide-like,26 although a substrate-competitive JAK2 inhibitor reached clinical trials,27 but has not progressed to launch. 

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