Drug discovery (lecture 9 +10) Flashcards
Describe the drug discovery process steps
- Identify disease
- Target identification validation
- Identify lead molecules
- optimise lead molecules
- preclinical trials
- clinical trials
- approval and circulation
Why is it difficult to design a drug?
because a good drug molecule needs to be able to have good efficacy at a minimal dose AND be safely administered.
How do we do target validation?
- using cell based assay
- Human mutations are introduced into mice
What is serendipity?
the discovery by accident
Describe some drugs that were discovered by chance?
- Penicillin (antibiotic)
- Meprobamate (Tranquilliser)
- Chlorpromazine (anaesthetic)
- Imipramine (depression)
Describe the process of screening in the identification of lead molecules ?????
High throughput screening
natural products
designed libraries
Screening small fragments (low MW compounds)
Describe processes that are used in the rational drug design process
XRAY crystallography and molecular modelling
Describe some parameters that determine the properties of a drug
- MW
- Number of H bond acceptors/donors
- lipophilicity (LogP, LogD)
- Acidity/ basicity (pKa)
- Solubility
- Polar surface area (PSA)
** These properties can be calculated before compounds are prepared.
Describe the properties of a potential candidate drug
A molecule that has the best balance of:
- Potency at & selectivity for target
- Appropriate stability & distribution in the body
- Efficacy in models of disease
- Lack of toxicity or other effects
- Potential for development into a medicine
What must an oral drug be able to do?
- Dissolve
- Survive a range of pHs
- Cross membranes
- Optimal delivery to site of target organ
- Avoid going into undesired places
What is 1st pass metabolism?
Being able to pass through the liver - an oral drug must be able to do this
What is 2nd pass metabolism?
Renal and biliary excretion - an oral drug must be able to AVOID this.
Describe preclinical trials
- Testing the safety and efficacy of the candidate drug
- Does the drug work in animal models?
- Is it safe in high doses in rats and a second species such as a dog?
Describe the different phases in a clinical trial
- Phase I – Healthy normal volunteers:
Is the drug safe and well-tolerated?
- Phase II – Patient population:
Does the drug work and if so, what is the best dose?
Phase III – Large patient population:
Does the drug work and is it better than current standard of care?
Side notes
Slide 21 on lecture (don’t know what we need to know from it)
- sometimes, clinical trial phases fail and it can result in death. (don’t know if we need to know the specific examples he gave, email and ask? Slides 25-29)
- table on slide 41
- Flow chart on slide 42
- slide 46
- I stopped making notes from slide 41 onwards whoops lo;
