Activity 3
Hit/lead identification
DNA-encoded library (DEL) screening and hit-to-lead optimization, mode-of-action and toxicity studies
Activity leader: Anne Marinier
Anticipated output
DNA-encoded libraries and peptide libraries for antibiotic screening
Validated bacterial targets and lead compounds
High-throughput metabolomic profiling of toxicity and drug efficacy
Platform development
DNA-encoded libraries for hit/lead identification and optimization
DEL construction,
hit-to-lead optimization
Metabolomics and efficacy and toxicity profiling
Preclinical validation
Mass spectrometry and automation
Robotics for metabolomics
DNA-encoded compound libraries identify target-binding hits
DNA-encoded compound libraries and machine learning
Metabolomic screening and hit-to-lead optimization
~90% of preclinical drug candidates fail in human clinical trials due to high toxicity, low efficacy, or poor pharmacokinetics.
The prevalent standard of animal testing is a poor predictor of downstream trial success.
High-throughput metabolomic approaches provide a comprehensive view of human cell/tissue responses to hits for optimization into leads.
Structure Activity Relationship (SAR) improvements
