In collaboration with several Principal Investigators at the CCR/NCI, <em>in silico</em>screening of large small-molecule databases are being conducted for a number of molecular targets relevant for cancer. We are using the <A HREF="""""""""""""""">CADD Group's</a>resources, including our screening <A HREF="""""""""""""""">databases</a> to generate lists of compounds to be purchased from <A HREF= """""""""""""""">commercial suppliers</a>, with the goal of obtaining novel lead compounds in <em>in vitro</em>and/or cell-based assays. <BR>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 &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. <BR>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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Scientific Cores Intramural Research (ZIC)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Cancer Institute Division of Basic Sciences
Zip Code
Jun, Jung Ho; Kumar, Vineet; Dexheimer, Thomas S et al. (2018) Synthesis, anti-cancer screening and tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibition activity of novel piperidinyl sulfamides. Eur J Pharm Sci 111:337-348
Zlotkowski, Katherine; Hewitt, William M; Yan, Pengcheng et al. (2017) Macrophilone A: Structure Elucidation, Total Synthesis, and Functional Evaluation of a Biologically Active Iminoquinone from the Marine Hydroid Macrorhynchia philippina. Org Lett 19:1726-1729
Shrimp, Jonathan H; Sorum, Alexander W; Garlick, Julie M et al. (2016) Characterizing the Covalent Targets of a Small Molecule Inhibitor of the Lysine Acetyltransferase P300. ACS Med Chem Lett 7:151-5
Montgomery, David C; Sorum, Alexander W; Guasch, Laura et al. (2015) Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors. Chem Biol 22:1030-1039
Zakharov, Alexey V; Peach, Megan L; Sitzmann, Markus et al. (2014) A new approach to radial basis function approximation and its application to QSAR. J Chem Inf Model 54:713-9
Zakharov, Alexey V; Peach, Megan L; Sitzmann, Markus et al. (2014) QSAR modeling of imbalanced high-throughput screening data in PubChem. J Chem Inf Model 54:705-12
Weidlich, Iwona E; Filippov, Igor V; Brown, Jodian et al. (2013) Inhibitors for the hepatitis C virus RNA polymerase explored by SAR with advanced machine learning methods. Bioorg Med Chem 21:3127-37
Geczy, Tamas; Peach, Megan L; El Kazzouli, Saïd et al. (2012) Molecular basis for failure of ""atypical"" C1 domain of Vav1 to bind diacylglycerol/phorbol ester. J Biol Chem 287:13137-58
Yao, Zhiyi; Xu, Yingjun; Zhang, Minmin et al. (2011) Discovery of a novel hybrid from finasteride and epristeride as 5?-reductase inhibitor. Bioorg Med Chem Lett 21:475-8
Liao, Chenzhong; Park, Jung-Eun; Bang, Jeong Kyu et al. (2010) Exploring Potential Binding Modes of Small Drug-like Molecules to the Polo-Box Domain of Human Polo-like Kinase 1. ACS Med Chem Lett 1:110-114

Showing the most recent 10 out of 22 publications