Drug Targets Flashcards
What is empirical drug discovery?
Recognises initial drug lead by functionally useful effect
eg. penicillin
What is rational drug discovery?
Drug by design or screen against biochemical target’s function
eg. HIV-protease inhibitor
What are the major causes of drug failure in Phase II?
Wrong target?
Wrong patient population?
Wrong dose?
What is a drug target?
Bio-molecule which either: Present in diseased molecule Elevated expression in diseased tissue Overreactive in diseased tissue Has involvement in disease process
What are the targets?
Enzymes Receptors Viral surface proteins Ion channels Transporters Nucleic acids
What are the mechanisms?
Reversible + irreversible reactions Agonists + antagonists Block entry into cell Block or open channel Block or promote transport Inhibit function/prevent gene expression
How do companies choose the disease to target?
Diseases that have fewer treatment options
Economic + medical factors considered
Important in developed world
What makes a good target?
Differentially expressed
Central to disease process with robust studies
Characterised in terms of expression, activity, function + role
What is target validation?
The process of demonstrating that engaging the target provides statistically meaningful therapeutic benefit with acceptable safety for given indication
What is a valid target?
A target when modulated pharmacologically, provides meaningful efficacy + acceptable safety for specific human disease in long term
How do you identify the target?
Genomics = RNA
Proteomics = target protein
Genetic association = DNA
How do you identify a valid target?
Genetics Clinical data Expression patterns In vitro models In vivo models Model organisms
How do you identify an actual drug target?
Detection of “new” drug target in samples of diseased tissue
Compare expression of “new” targets in clinical samples
Creation of test model
What happens if there is a greater drug selectivity for its target?
Less undesirable side effects
What should inhibitors only hit?
Target enzyme
