In collaboration with several Principal Investigators at the CCR/NCI, in silico screening of large small-molecule databases are being conducted for a number of molecular targets relevant for cancer. We are using the CADD Group's resources, including our screening databases to generate lists of compounds to be purchased from commercial suppliers, with the goal of obtaining novel lead compounds in in vitro and/or cell-based assays.? ? Currently, we are predominantly working on the targets Akt (PH domain), in collaboration with Phillip Dennis, Cancer Therapeutics Branch, CCR, NCI; c-Met, in collaboration with Donald Bottaro, Urologic Oncology Branch, CCR, NCI; and HSP90, in collaboration with Len Neckers, Cell & Cancer Biology Branch, CCR, NCI.? ? For both Akt and c-Met, initial hit sets have been generated, screening samples purchased, and these samples assayed by our collaborators. First results show inhibitory activity for a number of samples in either assay.