The main objective of the Assay Development Core is to develop and validate high-throughput (HTS) compatible assays that could facilitate discovery of new treatments for neurological diseases. The Assay Development Core has partnered with the Center for Integrative Chemical Biology and Drug Discovery (CICBDD) and the NIMH Psychoactive Drug Screening Program (PDSP) at UNC to provide neuroscience investigators access to the expertise and equipment needed to develop and validate HTS compatible assays. Specifically, this Core provides the following services:
1) Assay Development
a. Consultation. Investigators should contact Core Director, Dr. William Janzen, to discuss the development of an assay and its feasibility for adaption to HTS. These assays can be either cell-free (e.g. with purified proteins or cell extracts) or cell-based (e.g. involving a fluorescence or luminescence-based signal or a morphological readout).
b. Development and Validation of the assay. The Core will specifically help with the following: 1) adapt the assay for screening on a 96- or 384-well microplate format; 2) optimize the assay such that it meets the statistical thresholds for robotic screening (e.g. Z’-factor value of greater than 0.5); 3) evaluate other parameters such as tolerance to DMSO, stability of components, and position on plate variability.
2) Pilot Screens with Compound Libraries
The Core will conduct pilot screens with small-scale libraries with assays that have been developed for HTS. Three libraries for pilot studies are available within CICBDD:
1) LOPAC set (1280 compounds). These are a library of pharmacologically active compounds from Aldrich that includes 300 FDA approved drugs. These are known to target a variety of diverse cellular pathways including Gene Expression, Multi-Drug Resistance, Apoptosis, Ion Channels, Neurotransmission, Calcium Signaling, Lipid Signaling, and Phosphorylation.
2) Kinase targeted set (4727 compounds)–These compounds were selected based upon kinase pharmacophore-based searching and selection from various commercial vendors.
3) Epigenetic targeted compounds set (~1400 compounds). These have been selected from hits obtained from epigenetics-focused HTS projects undertaken at CICBDD.
3) Consultation for i) medicinal chemistry for analysis and prioritization of lead compounds from pilot screens, and ii) planning the next steps for translational drug discovery.