Current, typical path for drug discovery

Assay for molecular or cellular target: Read-out has high signal strength but relationship to underlying biochemistry and cell biology is unexplored

HTS carried out with robotics-friendly assay; Cut-off determined arbitrarily e.g. 50% inhibition or stimulation

Compounds picked for follow-up based strictly on IC50

Results: a few poorly-behaved templates

Knowledge-Based Decision Making Drug Discovery Path

Assay based on understanding biochemistry and/or cell biology and relationship between signal strength and biology is well understood

HTS carried out so that probabilities of detecting compound templates with particular affinities is calculated and available; HTS assay ready to be used for high-throughput secondary screening and characterization, especially high-throughput dose-response analyses

Compounds picked as templates based on dose-response analyses using information beyond the IC50

Results: a few well-behaved and promising templates