Drug design

Question 1

What is a pharmaceutical drug?

Answer 1

• Pharmaceutical drugs/medicines are chemicals that are used interfere with
  the process of human disease

USES and Examples:
- treat the symptoms of a disease - cold medication
- cure a disease - antibiotics
- prevent a disease - beta-blockers
- diagnose a disease - antibodies

Question 2

3 main sources of pharmaceutical drugs

Answer 2

1. Natural products pre-existing in nature
2. Chemicals –- i.e small molecules synthesized in the lab
3. Genetically engineered bioactive molecules called biologics, (typically
   human proteins), synthesised in the lab

Question 3

Mode of Action (of a drug)

Answer 3

refers to a functional or anatomical change
at the cellular level, resulting from the exposure of a living organism to a
pharmacological substance. (What does it do?)

Question 4

Mechanism of Action

Answer 4

refers to the molecular and
biochemical events through which a dug produces its pharmacological
effect (HOW does it do it?)

Question 5

What makes a good drug target?

Answer 5

1. Target has a proven function in the development of the disease
2. Target is less important under normal physiological conditions or in
   other diseases
3. Target expression is NOT uniform throughout the body
4. The 3D structure of the target, or a very close homologue is available
5. There exists a simple assay to monitor the activity of the target
6. The target activity has a broad dynamic range that can be manipulated
7. The potential side effects of modulating the activity of the target have
   been investigated and are predicted to be minimal.

Question 6

Drug Target

Answer 6

a biomolecule that undergoes a specific interaction with a
drug, resulting in a pharmacological effect on a particular disease

Question 7

Main classes of drug targets

Answer 7

1. Enzymes
2. Metabolites
3. Membrane structures, such as ion channels, receptors and transport proteins
4. DNA, RNA and the ribosome

Question 8

Why are membrane structures favoured as drug targets?

Answer 8

1. Given they control what enters and exits a cell they are key
   components of cell signaling pathways
2. Membrane receptors are highly specific for particular molecules and
   therefore drugs can be highly selelective for particular receptors
3. Not all cells have the same receptors and channels, so drugs can
   target specific cell types or tissues.
4. Membrane channel and receptor activities can be modulated in
   different ways

Question 9

Binding Site

Answer 9

the area on the
target that is bound by the drug.
* Drugs can act competitively or non-competitively to elicit an effect

Question 10

Drug Selectivity

Answer 10

refers to how well a drug
binds to one, and only one drug target.
The more selective the drug is the better

Question 11

Drug specificity

Answer 11

how specific is the effect that a drug ellicits

Question 12

1. Rational drug design

Answer 12

Rational drug design is the process of designing a new drug based on the
molecular knowledge of the potential drug target “intelligent design”

Question 13

2. Computer aided drug design

Answer 13

is used to design a potential drug based
on the molecular structure of either:
* the drug target
* a known ligand of the drug target

Question 14

3. Large Scale unbiased compound screening

Answer 14

Pharmaceutical companies typically have libraries/bank of natural and
synthetic compounds (>100,000+) that they screen through one by one to see
if it has the desired effect