Drug discovery - Week 2 History, Intro and Biologics and Pharmaceuticals of Drugs

Question 1

What is a drug in pharmacology? (5)

Answer 1

A chemical entity of known structure which causes a biological effect when administered to a living system. Including:
- regulated therapeutic compounds - - experimental compounds and drug candidates
- toxins/poisons unregulated
- “recreational” and “performance-enhancing” substances

Question 2

What is a drug in the pharmaceutical industry? (2)

Answer 2

A single chemical substance that represents the active ingredient of a regulated product (a pharmaceutical medicine) which can be conventionally marketed for use in clinical therapy

Question 3

What is SAR? (1)

Answer 3

The relationship between the chemical structure of a drug and its biological activity

Question 4

What is target identification? (3)

Answer 4

Analyse the pathophysiological pathways underlying the disease and identify “amenable” macromolecules that could be targets
Knock-outs or known targets of other drugs may help the decision

Question 5

What is target validation? (3)

Answer 5

Finding a drug that affects a target is pointless if this does not translate into efficacy in the clinic
Evidence from other approved drugs that act via the same target is clear evidence but more difficult if it is a novel target
Using in vivo disease models (perhaps a knock-out/transgenic) may be convincing

Question 6

For small molecule discovery, what are the 3 main components (3)

Answer 6

Finding the starting compound
Finding the lead compounds
Optimising the leads to produce a single development candidate compound

Question 7

Describe Lead Finding via SAR cycling (3)

Answer 7

There may be several different classes of starting compounds at the start, from which “focussed libraries”, encompassing multiple variations of each class of starting compound, can be synthesised.
By cycling around the “SAR engine” we can learn more and more about the pharmacophore.
Eventually, the best candidate is classed as the “lead compound” and taken forward for “optimisation”.

Question 8

What is lead optimisation? (2)

Answer 8

Improving the drug-like properties of the compound rather than simply the compounds potency
It is balancing the drug’s efficacy with its metabolism pharmacokinetics

Question 9

What determines the efficacy of a drug? (1)

Answer 9

Concentration of the drug at its target site

Question 10

What impacts the efficacy of a drug? (4)

Answer 10

ADME
Absorption
Distribution
Metabolism
Excretion