Discovery of small molecule inhibitors targeting the SUMO-SIM interaction using a protein interface consensus approach

The SUMO-SIM is a challenging protein-protein interaction drug target. We present a virtual screening approach incorporating the consensus of protein interactions that led to the discovery of non-peptidic inhibitors. The most potent inhibitors have low micromolar potency and the binding affinity and interface was validated using multiple assays and HSQC-NMR.