Developing new therapies Lecture 22

Question 1

What is the first step of drug development?

Answer 1

1. Drug Discovery
   -Identify appropriate therapeutic target
   Lead identification:
   -Identify ‘hits’ using high throughput screening: molecules with activity against the target
   Lead optimisation:
   -Hits generated by screening retested using range of conc. and assays. The lead hit will be selective and have good solubility
   -Pharmacokinetics important for further tests: ADME (absorption, distribution, metabolism and excretion)
   -General guidelines exist (5 H bond doners max, 10 H bond acceptors max)
   Find drug with:
   -Oral availability >50%
   -Activity such that dose is ideally <100mg daily
   -T1/2 clearance >3hrs

Question 2

What is the second step of drug development?

Answer 2

2. Drug Development
   -Phase 1 trials to seek maximum tolerated dose and study pharmacokinetics and pharmacodynamics (effects of drug on target)
   -Best route of administration considered
   Costs - big problem as many trials make it to phase II but not to phase III