Theme 5: Lecture 1

Question 1

What is lead optimisation?

Answer 1

The process of designing and improving a preidentified lead compound.

1. Initially involves in vitro (outside normal biological context) assays, the secondary assays
2. Progression to in vivo animal models

Question 2

What is the aim of lead optimisation

Answer 2

Aims to deliver one or more clinical candidate drug nominations

Question 3

What should a clinical candidate drug have (desires for a good clinical candidate)?

Answer 3

• Selectivity (Able to bind to specific drug-target)
• Potency (amount of drug required to produce an effect of a given magnitude)
• Efficacy (Drugs ability to produce a pharmacological response)
• Physical and pharmaceutical properties
• Optimal safety profile

Question 4

When it comes to lead optimisation, what 3 main activities are we optimising?

Answer 4

• Drug-drug interaction, via biological activity of synthesised compounds in primary /secondary assay
• Optimisation of drug-like properties
• In vitro testing for toxicity/safety leading to preclinical studies and drug development

Question 5

How is affinity measured?

Answer 5

Equilibrium dissociation constant (Kd)

Question 6

What is the equation for dissociation constant?

Answer 6

Kd= [D][P]/[DP]

Question 7

True or false?
There is a continuous turnover of bound and nonbond drug-protein complexes in an equilibrium?

Answer 7

True

Question 8

Kd will increase (e.g. affinity of a drug) if DP is a large number (true or false?)

Answer 8

true