1.2 Drug Discovery
Drug discovery is the process of identifying new medication candidates. Modern approaches combine target-based screening, structure-based design, and AI-driven methods.
Target Identification
Genomics & Proteomics
Identify disease-associated genes and proteins. GWAS, expression profiling, functional genomics.
Target Validation
Confirm target role in disease: knockout models, siRNA, CRISPR, antibody blockade.
Druggability Assessment
Evaluate if target can be modulated by small molecules or biologics. Binding site analysis.
Hit Finding Methods
High-Throughput Screening (HTS)
Test millions of compounds against target. Automated assays, robotics, detection systems.
Virtual Screening
Computational screening of compound libraries. Docking, pharmacophore modeling, ML methods.
Fragment-Based Drug Discovery
Start with small fragments (~150 Da), build up. NMR, X-ray crystallography guided.
Natural Products
Bioactive compounds from plants, microbes, marine organisms. ~50% of approved drugs.
Lead Optimization
SAR Studies
Structure-Activity Relationships: systematic modification to improve potency, selectivity, ADME.
ADMET Optimization
Improve absorption, distribution, metabolism, excretion, toxicity properties.
Lipinski's Rule of Five
MW ≤500, logP ≤5, H-bond donors ≤5, H-bond acceptors ≤10. Oral bioavailability predictor.
Modern Approaches
AI/Machine Learning
AlphaFold for protein structures, generative models for novel molecules, property prediction.
DNA-Encoded Libraries
Billions of compounds tagged with DNA barcodes. Affinity selection, sequencing identification.
Phenotypic Screening
Cell-based assays measuring disease-relevant phenotypes, target-agnostic approach.
PROTAC Technology
Targeted protein degradation. Bifunctional molecules recruit E3 ligase to target protein.