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High Throughput Screening and Assay development for Drug Discovery

Across
Test performed in a living system • Animal Toxicity Acute toxicity Chronic toxicity • Pre-Clinical Trials • Clinical Trials
Microchips lined by living human cells that could revolutionize drug development, disease modelling and personalized medicine
➢ Ligand based or Target based ➢ Target Selection ➢ Data Mining (Chemical space of over 1060 conceivable compounds) ➢ Screening of Libraries of Compounds Virtually ➢ Lead Identification ➢ Prediction of Structure-Activity Relationships ➢ It saves Time, Money and Efforts
Cytotoxicity Apoptosis Whole-cell-ligand-binding Ion channel Transporters Bead-based MRNA assay GPCR Translocation Reporter gene
Target Identification> target validation> assay development> lead optimisation> development
Software packages for HTS (e.g. Activitybase, Spotfire) are available to carry out the principle tasks like a) Storage of raw data b) Quality control c) Transformation of data into information d) Documentation e) Reporting
o Animal-based assays (In Vivo) o Toxicological Assessments in whole animals o ADME Studies o Behavioral Studies o Preclinical Studies
o Non- physiological Assays o Biochemical or Mechanism- Based Assays o Microorganism-based bioassays o Cell-based Bioassays o Tissue-based Bioassays o Many other In Vitro bioassays/assays
Target Identification> target validation> assay development> HTS(hit validation)> lead identification> lead optimisation[Chemistry, structure activity re relationship SAR, bioavailability, PK, ADME, toxicity, in vivo efficacy)> DEVELOPMENT (pre-clinical and clinical)
Down
experimental situation outside the organisms Biological or chemical work done in the test tube rather than in living systems • Toxicity Assays • MTT assay • Cancer cell line assays
• Virtual Screenings • Primary Bioassays • Secondary Bioassays • Preclinical Trials • Clinical Trials
Primary assays HTS and selective library screens; structure based design Reiterative directed compound synthesis to improve compound properties Secondary assays In virtual and ex vivo secondary assays(mechanistic) Selectivity and liability assays
Robotics ❖ Miniaturization ❖ Sophisticated Assay Chemistry ❖ Sophisticated Software and Database Robots perform assay in microtiter plates
Bioassay or biological assay/screening is any qualitative or quantitative analysis of a substance that uses a living system, such as an intact cell, as a component.
Relevant; relevant to the target Robustness; is the assay giving similar results without fluctuation Reliability/reproduceability; similar results with the same compounds Practicality/feasibility; too difficult to take to the next mode Cost Automation; it be automated
Compound which has the desired activity in a compound screen and whose activity is confirmed upon retesting