Drug Development Flashcards
What are the four main stages of drug development?
drug discovery, preclinical development, clinical development, regulatory review
Stages of drug discovery
target selection, lead finding, lead optimisation
targets for drugs
enzymes, transport proteins and receptors
First step of target selection
target identification
What does target identification involves
coupling genomic data with disease mechanisms and signalling pathways
What limits innovation of drugs
poor target selection, unforeseen side effects
What are lead compounds derived from
synthetic chemistry
What helps find the lead compound
cloning and expression of target protein
Why is cloning and expression of the target protein done in human form
variations between species can lead to pharmacological differences
What techniques does lead finding use?
assays
What do assays in lead finding measure
functional activity of the target protein
What do lead finding assays require
large compound libraries
How are the large compound libraries made
combinatorial chemistry
What techniques are used to gain knowledge about the target
molecular modelling and X-ray crystallography
What are undesirable characteristics of a drug
large molecular weight, large polarity, toxicity
What eliminates undesirable drugs
computational screening of compound libraries
What are the aims of lead optimisation
increase potency, optimise selectivity and pharmacokinetic properties
What do assays at the stage of lead optimisation measure
activity and time course
What are the four main catergories of preclinical development
pharmacological, preliminary toxicological, pharmacokinetic testings
What do tests during preclinical development check for
side effects, absorption, maximum non-toxic dose,
What does preclinical development stage have to conform to
good labrotory practice
What does phase I of clinical trials check for
dangerous side effects and pharmacokinetic properties
What dose clinical trial phase II determine
beneficial pharmacodynamic effects
What does clinical trial phase III involve
randomised trials of drug versus a placebo
What does clinical trial phase IV involve
detection of unwanted long term adverse effects
How are biopharmaceuticals produced
biotechnology
What is an advantage of biopharmaceutical versus convential synthetic compounds
they have less toxicological problems
What are the disadvantages of biopharmaceuticals versus conventional drugs
more problems relating to production, quality control, immunogenicity and delivery
What can biopharmaceuticals be used to treat?
cancer
What is benefical about biopharmaceuticals
high affinity binding, specific and targeted
What can cause drug withdrawal
long term adverse effects, lack of expected effect on target, toxicity
