This application proposes to establish a Molecular Libraries Screening Center (UP-MLSC) exploiting existing and new space and facilities at the University of Pittsburgh, with membership from the University of Pittsburgh, Carnegie Mellon University and Sandia National Laboratories. The overall objective of the UPMLSC will be to develop, implement, and optimize robust, optical methods for the detection, characterization, and refinement of small molecules with desired biological and pharmacological properties in cell-free, cell-based, and model organism-based assays assigned by the MLSCN Steering Group. The goals of the UPMLSC will be (a) to validate assays for use in high throughput screening, (b) to use these assays with secondary assays and informatics to identify active small molecules from chemical libraries, (c) to facilitate the use of these assays nationally, (d) to disseminate information about compound activity, and (e) to assist in the further optimization of the lead compounds. We intend to exploit and expand the documented existing interactive strengths of the Center members in assay implementation, high throughput and high content screening, combinatorial chemical synthesis, and informatics. We have carefully selected members for the UP-MLSC because of their expertise in the above-mentioned Core areas and in anticipation of potential assays that will be submitted to the Center. Moreover, we have recruited individuals who are expert in the design and development of novel fluorescent probes that may be useful in implementing new HTS assays, and individuals who have experience with assay development with Drosophila and zebrafish, which will be the models for organism-based assays in the UP-MLSC. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
3U54MH074411-03S1
Application #
7502274
Study Section
Special Emphasis Panel (ZMH1-ERB-Y (02))
Program Officer
Brady, Linda S
Project Start
2005-07-01
Project End
2009-06-30
Budget Start
2007-09-27
Budget End
2009-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$160,309
Indirect Cost
Name
University of Pittsburgh
Department
Pharmacology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
George Rosenker, Kara M; Paquette, William D; Johnston, Paul A et al. (2015) Synthesis and biological evaluation of 3-aminoisoquinolin-1(2H)-one based inhibitors of the dual-specificity phosphatase Cdc25B. Bioorg Med Chem 23:2810-8
Johnston, Paul A; Shinde, Sunita N; Hua, Yun et al. (2012) Development and validation of a high-content screening assay to identify inhibitors of cytoplasmic dynein-mediated transport of glucocorticoid receptor to the nucleus. Assay Drug Dev Technol 10:432-56
Shun, Tong Ying; Lazo, John S; Sharlow, Elizabeth R et al. (2011) Identifying actives from HTS data sets: practical approaches for the selection of an appropriate HTS data-processing method and quality control review. J Biomol Screen 16:1-14
Sharlow, Elizabeth R; Mustata Wilson, Gabriela; Close, David et al. (2011) Discovery of diverse small molecule chemotypes with cell-based PKD1 inhibitory activity. PLoS One 6:e25134
Johnston, Paul A (2011) Redox cycling compounds generate H2O2 in HTS buffers containing strong reducing reagents--real hits or promiscuous artifacts? Curr Opin Chem Biol 15:174-82
Bravo-Altamirano, Karla; George, Kara M; Frantz, Marie-CĂ©line et al. (2011) Synthesis and Structure-Activity Relationships of Benzothienothiazepinone Inhibitors of Protein Kinase D. ACS Med Chem Lett 2:154-159
Sharlow, Elizabeth R; Lyda, Todd A; Dodson, Heidi C et al. (2010) A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity. PLoS Negl Trop Dis 4:e659
Dudgeon, Drew D; Shinde, Sunita; Hua, Yun et al. (2010) Implementation of a 220,000-compound HCS campaign to identify disruptors of the interaction between p53 and hDM2 and characterization of the confirmed hits. J Biomol Screen 15:766-82
Soares, Karina M; Blackmon, Nicole; Shun, Tong Ying et al. (2010) Profiling the NIH Small Molecule Repository for compounds that generate H2O2 by redox cycling in reducing environments. Assay Drug Dev Technol 8:152-74
LaValle, Courtney R; George, Kara M; Sharlow, Elizabeth R et al. (2010) Protein kinase D as a potential new target for cancer therapy. Biochim Biophys Acta 1806:183-92

Showing the most recent 10 out of 31 publications