Virtual screening is becoming a powerful tool for lead identification.Although numerous examples of structure-based or pharmacophore-based virtual screening have been reported, successful stories of lead-to-candidate-to-drug are still limited.1 In this regard, integrating virtual screening with synthetic medicinal chemistry can be a useful strategy to select and optimize hits from virtual screening.Our group have performed several successful virtual screening and hit optimization studies toward important antitumor targets such as toposimerase Ⅰ/Ⅱ and p53-MDM2.2-4 A series of highly potent antitumor lead compounds were identified and several of them are under early preclinical evaluation.