Identification of novel inhibitors of extracellular signal-regulated kinase 2 based on the structure-based virtual screening

Extracellular signal-regulated kinase 2 (ERK2) has become an attractive target for the development of therapeutics for the treatment of cancer. We have been able to identify eight new inhibitors of ERK2 by means of a drug design protocol involving the virtual screening with docking simulations and in vitro enzyme assay. The newly discovered inhibitors can be categorized into three structural classes and reveal a significant potency with IC50 values ranging from 1 to 30 μM. Therefore, all of the three inhibitor scaffolds deserve further development by structure–activity relationship or de novo design methods. Structural features relevant to the stabilizations of the newly identified inhibitors in the ATP-binding site of ERK2 are discussed in detail.

Graphical abstractWe have discovered three novel inhibitor scaffolds for extracellular signal-regulated kinase 2 (ERK2) by means of a drug design protocol involving the virtual screening with docking simulations and in vitro enzyme assay.Figure optionsDownload full-size imageDownload as PowerPoint slide