Otradi
Oregon Translational Research and Drug Development Institute (OTRADI)
OTRADI leverages its core assets and capabilities — the Oregon Collection compound library; multiple commercial compound libraries; a state-of-the-art, high-throughput screening system capable of testing tens of thousands of compounds per day; cutting-edge, high-content screening for drug mechanism of action studies; and an arsenal of experimental assays designed to effectively screen compounds for activity against a wide range of disease targets— to provide value-added experimental data to fuel drug discovery.
OTRADI's capabilities span many steps in the drug development process, including: assay development, compound screening to identify "hits," dose-response and toxicology profiling for compounds of interest, lead optimization, and preclinical models.
Compound Libraries & Collections
- Amassing "Oregon Collection" of novel natural and synthetic compounds from researchers across Oregon's research universities
- Screening several large commercially available compound libraries of interest
- Building a comprehensive compound library of novel and known compounds, with the goals of identifying unique chemical properties, generating and validating hits, and optimizing leads
OTRADI Compound Activity Pipeline
- Building a searchable, fully-integrated database to assess each compound's chemical structure, unique properties, and full range of activity in all assays run at OTRADI
- Providing feedback to chemists on compound activity to assist in designing derivatives
High-Throughput Screening Assays Completed to Date:
- Anti-Cancer Assays:
Compounds are screened according to protocols derived from the National Cancer Institute, as found here: http://dtp.nci.nih.gov/branches/btb/ivclsp.html . Appropriate target cancer cell lines are determined and added after discussion with participating investigators. - Cytotoxicity Assays:
Adverse effects on viability of human cells are defined in a dose-responsive manner for each compound assayed. We determine cytotoxicity using an assay that quantitates how chemical compounds affect mitochondrial health within mammalian cells. Cytotoxicity is indicated by the number/proportion of damaged and nonviable cells, which will have lower innate metabolic activity and thus generate a proportionally lower signal than healthy cells. - Custom Assay Development:
OTRADI works with investigators on a case-by-case basis to customize assays for novel targets and/or to optimize an investigator's assays to be more amenable to high-throughput screening or high-content analysis. - Anti-Malarial Assays:
Compounds are added to human blood infected with Plasmodium falciparum in a microplate format. Each compound is analyzed for anti-malarial activity in comparison with positive controls, including the known anti-malarial drug artemisinin. - Anti-Bacterial Assays:
Compounds are added to dilute bacterial cultures containing either Escherichia coli (E.coli) or Staphylococcus aureus (S.aureus) in a microplate format. Each compound is analyzed for the ability to block growth of E.coli and/or S. aureus in comparison with positive controls, including known anti-bacterial drugs (e.g., ampicillin, penicillin, gentamicin). - Anti-Fungal Assays:
Compounds are added to dilute fungal cultures containing Aspergillus flavus (A.flavus) in a microplate format. Each compound is analyzed for the ability to block growth of A.flavus in comparison with positive controls, including the known anti-fungal drug amphotericin B.
High-Content Analysis and Screening
- Simultaneously screen for and prioritize hits based on each compound's specificity for a given target, as well as its lack of overall cytotoxicity
- Enable mechanism of action studies to analyze compounds' effects on cells
- Provide imaging and analysis of live and fixed cells
- Design and run kinetic assays to image the same cells over an extended time course to assess when compounds are active in the cell
- Identify cellular and enzymatic targets for drugs