We have over 350 cell lines available, both prokaryotic and eukaryotic.
In 2005, Scripps Florida created the Translation Research Institute, which has capabilities for several aspects of early-stage drug discovery, including Assay Development, including Cell Lines, HTS Campaigns, Compound Management, Cheminformatics and Instrumentation Development.
Overview of The Molecular Screening Center
The Molecular Screening Center is a collaborative effort between biology, engineering, information technology, chemistry and pharmacology staff. The first step of Lead Identification is called “Assay Development” [Step 1]. Assay development starts with the nomination of a relevant “target” (for example, a kinase, G-protein coupled receptor, pathogenic bacterial strain) and the creation of an “assay” (experiment) that enables the testing of compounds for pharmacologic activity against that target. To maximize throughput and economy of a high-throughput screening (HTS) campaign, the assay is adapted to microtiter-plates and validated for HTS using specialized equipment. After completion of this step, the assay is considered “HTS-ready.” It is then mounted on our fully-automated screening platform, and the “HTS Campaign” begins [Step 2]. During the HTS campaign, each compound in our 600,000-member collection is screened against the target, with the ultimate goal of discovering compounds with pharmacologic activity against the target. All data emerging from HTS is uploaded to our corporate databases for further processing.
After data passes Quality Control (QC) metrics, cheminformatics tools are implemented to prioritize compounds of interest. For example, these tools can be used to determine an active compound’s selectivity to the target, cytotoxicity, structure-activity relationships (SAR) or even physical parameters such as solubility and logP values. Upon completion of analysis, compounds are gathered for further testing in Lead Optimization assays that confirm activity, profile selectivity, or determine mechanism of action [Step 3]. These compounds can come from Lead Identification’s library, be procured from vendors or even re-synthesized if not readily available.
A successful Lead Identification effort results in a set of well-characterized compounds, “Leads,” with promising SAR as well as desirable pharmacologic and physical properties. These compounds can then be further characterized and refined via downstream efforts, such as Medicinal Chemistry and DMPK, and in vivo studies. These activities can be executed in our collaborator’s lab, or within other facilities located at UF Scripps.