Structure-based virtual screening and biological evaluation of potent and selective ADAM12 inhibitors

The virtual screening for the potent and selective ADAM12 inhibitors (IC 50 ⩽ 50 nm) is reported. We describe a series of potent and selective inhibitors of ADAM12 that were discovered using computational screening of a focused virtual library. The initial structure-based virtual screening selected 64 compounds from a 3D database of 67,062 molecules. Being evaluated by a cell-based ADAM12 activity assay, compounds 5, 11, 14, 16 were further identified as the potent and selective inhibitors of ADAM12 with low nanomolar IC 50 values. The mechanism underlying the potency and selectivity of a representative compound, 5, was investigated through molecular docking studies.