Lecture 6: 11/10
Pharmacology its role in drug discovery
Introduc)on
- Pharmacology: effect of chemical substance (parent compound/ac;ve metabolites) on living
systems
- In vitro
o Selec;vity screening -> molecular target
o Pharmacological profiling
§ Primary: linked to the target
• Asses if the compound binds to the target
§ Secondary: linked to side effects
• Compound binds to other targets
o Screen several types of receptors
• Really important to assess
- In vivo
o Therapeu;c efficacy
o Safe pharmacology (toxicology) -> side effects
§ You will look if the compound interferes with the important func;ons, like for
example the brain func;on, the long func;on …
Pharmacological test system
- Hierarchy of op;ons
o Targets
§ Receptor present in a ELISA assay
o Cellular level
§ Immuno assays, flow cytometry
o Tissue and organs
o Animals
- Molecular/cellular assays
o Througput is high
o Quan;;ve precision is good
o The cost is low
o Generally inflexible
- In vitro pharmacology
o Throughput less
o Quan;ta;ve precision could be good, but you will get interference of covariant
o Cost is low, and you can adapt it
o You can this on human cell line -> you have the correct species
§ Not always representa;ve
- Whole animal
o Throughput is low
o You may have uncontrol PK and physiological factors
o Higher cost
o You can adapt, but you are limited by PK
, o You can have species differences -> not always representa;ve for what’s happening in
the human situa;on
o Animal models are good for liver toxicity, but for other types of toxicity is it less goof
- Disease models
o Cost are oYen very high
o Throughput low
General R&D posi)oning
- Selec;ve screening is very early
- Second PD: you have already a lead component
- Safety pharmacology: part of drug development process
Screening for selec)vity
- You can use different receptors
- Impact on several organs
- This early screens for all these receptors is important to know if you are going to have later
on a problem
- OYen forgo[en by biotech companies
- Do I have off target effects?
- You don’t want that people get a allergic reac;on when they take a drug -> histamine levels
Pharmacology its role in drug discovery
Introduc)on
- Pharmacology: effect of chemical substance (parent compound/ac;ve metabolites) on living
systems
- In vitro
o Selec;vity screening -> molecular target
o Pharmacological profiling
§ Primary: linked to the target
• Asses if the compound binds to the target
§ Secondary: linked to side effects
• Compound binds to other targets
o Screen several types of receptors
• Really important to assess
- In vivo
o Therapeu;c efficacy
o Safe pharmacology (toxicology) -> side effects
§ You will look if the compound interferes with the important func;ons, like for
example the brain func;on, the long func;on …
Pharmacological test system
- Hierarchy of op;ons
o Targets
§ Receptor present in a ELISA assay
o Cellular level
§ Immuno assays, flow cytometry
o Tissue and organs
o Animals
- Molecular/cellular assays
o Througput is high
o Quan;;ve precision is good
o The cost is low
o Generally inflexible
- In vitro pharmacology
o Throughput less
o Quan;ta;ve precision could be good, but you will get interference of covariant
o Cost is low, and you can adapt it
o You can this on human cell line -> you have the correct species
§ Not always representa;ve
- Whole animal
o Throughput is low
o You may have uncontrol PK and physiological factors
o Higher cost
o You can adapt, but you are limited by PK
, o You can have species differences -> not always representa;ve for what’s happening in
the human situa;on
o Animal models are good for liver toxicity, but for other types of toxicity is it less goof
- Disease models
o Cost are oYen very high
o Throughput low
General R&D posi)oning
- Selec;ve screening is very early
- Second PD: you have already a lead component
- Safety pharmacology: part of drug development process
Screening for selec)vity
- You can use different receptors
- Impact on several organs
- This early screens for all these receptors is important to know if you are going to have later
on a problem
- OYen forgo[en by biotech companies
- Do I have off target effects?
- You don’t want that people get a allergic reac;on when they take a drug -> histamine levels
