Intro to Drug Discovery Flashcards
What are the key stages of a typical drug discovery project?
Target Identification Hit and Lead Identification Lead Optimisation Pre-clinical Development Clinical Development Phase I, II, III Launch & Post Launch
What is target identification?
A critical stage involving identification of a target which are usually proteins
How can a target be further validated?
By looking at the impact of inhibiting or removing the protein in pre-clinical experiments
Give examples of sources of new chemical leads
Natural products
Virtual
Fragment or high throughput screening
Optimisation of known drugs
What is needed for a compound to progress to clinical trials?
It should have the desired biological effect in cell / animal models and should have suitable human pharmacokinetics
What happens in pre-clinical development?
Cross species animal toxicology studies can identity likely toxicological effects in humans and no observable adverse effect limits
What is Phase 1 in clinical development?
A demonstration of exposure and initial assessment of safety
What is Phase 2a in clinical development?
Proof of principle - does the drug alter the target
What is Phase 2b in clinical development?
Proof of concept - does drug induced alteration of the target have impact on disease progression
What is Phase 3 in clinical development?
Demonstration of efficacy and safety in a clinically relevant setting
What happens to drugs as lipophilicity increases?
They get more potent, less soluble, are more likely to be metabolised and likely to be toxic
How can the lipophilicity of a compound be measured?
By allowing it to partition between 2 immiscible phases
What does it mean if a compound has a LogD > 0?
More of the compound is in the ORGANIC phase than in the aqueous phase - drug is hydrophobic
What does it mean if a compound has a LogD < 0?
More of the compound is in the AQUEOUS phase - drug is hydrophilic
What is used for almost all LogD measurements?
N-octanol
