Drug Discovery 1&2 Flashcards
What are the 3 main sources of drugs?
- Natural compounds
- Small molecules (made synthetically, e.g. Gleevec)
- Recombinant products (i.e. monoclonal antibodies)
How long is the general drugs discovery pipeline?
25
What is IC50?
Te concentration of drug where you get 50% inhibition
What is the typical IC50 of an initial hit in the drug discovery pipeline?
IC50 = 1µM
What is a Hit?
Small molecule with some effect identified by biological and/or computational screening
What is the target?
protein or other molecule whose activity is to modified
What is a lead?
Chemical modification of a hit to enhance its effects and remove adverse effects in ADMET
What is an optimised lead?
- Potency of IC50 <1nM
- Selectivity of 1000 fold compared to similar receptor
- Solubility of <1mg/ml
- ADMET compliancy
- Safety demonstrated in animal
- Efficiency (Better than other drugs) in animal models
What is clinical phase 1?
Small no. of healthy people (20-80) to establish a safe dose
What is clinical phase 2?
Larger numbers of unhealthy patients (100-300) to firm up results from phase 1 and to establish level of effectiveness
What is clinical phase 3?
Thousands of unhealthy patients to prove drug is effective and identify side effects against placebo
What is the regulation phase of the drug discovery pipeline?
Approval for drug to be used and marketed
What is the ‘sales’ phase?
Also known as phase IV - monitoring side effects over years
What is the rough cost of the drug discovery pipeline?
Between $500 million to $1.5 billion
What is attrition rate?
The amount of molecules that are dropped during the drug discovery pipeline
Which is the most expensive phase of the drug discovery pipeline?
Clinical phase 3
What is Eroom’s Law?
The cost per drug production is increasing as efficiency decreases.
What does AMDET stand for?
Absorption Distribution Metabolism Excretion Toxicology