In collaboration with several Principal Investigators at the CCR/NCI, &lt;em&gt;in silico&lt;/em&gt;screening of large small-molecule databases are being conducted for a number of molecular targets relevant for cancer. We are using the &lt;A HREF="http://ccr.cancer.gov/staff/staff.asp?profileid=6282"&gt;CADD Group's&lt;/a&gt;resources, including our screening &lt;A HREF="http://ccrintra.cancer.gov/cms/annual_reports/projects/printer_friendly_report.asp?ProjID=6864"&gt;databases&lt;/a&gt; to generate lists of compounds to be purchased from &lt;A HREF= "http://www.chemnavigator.com/nih.asp"&gt;commercial suppliers&lt;/a&gt;, with the goal of obtaining novel lead compounds in &lt;em&gt;in vitro&lt;/em&gt;and/or cell-based assays. &lt;BR&gt;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 Terrence R. Burke, Jr., Laboratory of Medicinal Chemistry, CCR, NCI;HSP90, in collaboration with Len Neckers, Cell &amp;Cancer Biology Branch, CCR, NCI;polo-Box domain of polo-like kinase 1, in collaboration with Kyung S. Lee, Laboratory of Metabolism, CCR, NCI;Grb2 SH2 domain, in collaboration with Terrence R. Burke, Jr., Laboratory of Medicinal Chemistry, CCR, NCI;PKC, in collaboration with Peter Blumberg, Laboratory of Cancer Biology and Genetics, CCR, NCI, and Victor E. Marquez, Laboratory of Medicinal Chemistry, CCR, NCI;herpes thymidine kinase, in collaboration with Victor E. Marquez, Laboratory of Medicinal Chemistry, CCR, NCI;tyrosyl-DNA phosphodiesterase (Tdp1), in collaboration with Yves Pommier, Laboratory of Molecular Pharmacology, CCR, NCI, and Barbara Mroczkowski, Special Assistant to the Director, NCI, in the context of NCI's Chemical Biology Consortium;bis-imidazoacridone DNA intercalators, in collaboration with Sergey Tarasov, Structural Biophysics Laboratory, CCR, NCI;small-molecule mimetics of a surface patch of thrombospondin-1 (TSP1) interacting with CD47, in collaboration with David D. Roberts, Laboratory of Pathology, CCR, NCI;the interaction of the transcription factor HIF-1 alpha with cofactor p300, in collaboration with William Douglas Figg Sr., Medical Oncology Branch, CCR, NCI;and the aberrant chimeric transcription factor ASPL-TFE3, in collaboration with Robert H. Shoemaker, Screening Technologies Branch, DTP, DCTD, NCI. &lt;BR&gt;For Akt, c-Met, the polo-Box domain of plk1, Tdp1, and TSP1/CD47, initial hit sets have been generated, screening samples purchased, and these samples assayed by our collaborators. Inhibitory activity was found for a number of samples in each one of these assay. Sample sets have been proposed for purchase for the HSP90 project.