1. Bioinformatics in Drug Design
11/7/2018
Bioinformatics in Drug Design

2. Topics Drug Discovery Pipeline Databases Data processing/analysis
Network modeling/analysis
Rational/Structure-based design
Clinical Trials/Registration

3. Drug Discovery Pipeline
Target Discovery
Lead Finding/Discovery
Lead Optimization
Exploratory Development
Clinical Trials/Registration

4. Target Discovery Find out where to act Methods:
activate/repress receptor or enzyme?
different points in network?
Methods:
Metabolic/Regulatory Network analysis
Comparative Genomics
Homology Modeling
Microarray/CGA

5. Lead Finding/Discovery
Find ‘some’ molecule that does ‘something’ with your target:
bind
activate
repress
Methods:
HTS
Virtual screening
Combichem
Cheminformatics

6. Lead Optimization
Find better molecule that does exactly what you want, and nothing else
specific for target
possible side-effects
Methods:
Targeted screening
Rational/Structure-based design
QSAR
ADME(T) (Absorption, Disposition, Metabolism, Excretion, Toxicology)

7. Exploratory Development
Find out what your molecule does in ‘real life’
uptake, breakdown, toxicity
positive and negative effects
Methods:
Animal models
Gene markers
Expression profiles
‘Translational modeling’
from animal to human
(?) Pharmacokinetic modeling/ADME(T)

8. Drug Discovery Pipeline
target discovery
lead finding
lead optimization
exploratory development
clinical phase(s)
~14 years
~ $ 800 million

9. Bioinformatics in Pipeline
target discovery
lead finding
lead optimization
exploratory development
clinical phase(s)
network analysis
comparative genomics
microarray
microarray
CGA
CGA
homology modeling
homology modeling
SNPs/haplotypes
SNPs/haplotypes
virtual screening
molecular modeling
rational/structure based design
ADME(T)/pharmacokinetics modeling
animal models