Crystal structure of human ERK2 complexed with a pyrazolo[3,4-c]pyridazine derivative

A series of pyrazolopyridazine compounds were briefly investigated as ERK2 inhibitors. The crystal structure of ERK2 complexed with an allyl derivative was determined. The compound induces structural change including movement of the glycine-rich loop and peptide flip between Met108-Glu109. As a result, the newly formed subsite can recognize small hydrophobic substituents but not hydrophilic ones.

Graphical abstractA series of pyrazolopyridazine compounds were briefly investigated as ERK2 inhibitors. The crystal structure of ERK2 complexed with the allyl derivative provides structural insight which could be used in the design of more potent ERK2 inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide