Discovery

Question 1

what is a drug?

Answer 1

A product that alleviates, cures, or prevents disease, or is intended to affect the structure
or function of the body

Question 2

how long from initial “hit” do you think it takes a drug to get to market?

Answer 2

14 years

Question 3

what are the 3 ‘D’s?

Answer 3

Discovery Development Delivery

Question 4

Why do drugs fail?

Answer 4

• lack of biological activity
• cannot be used in humans
• not enough interest in compound
• lack of investment

Question 5

Target based

Answer 5

Targets a specific protein/pathway which is essential for disease

Targets are identified
- Use recombinant proteins
or cells over-expressing the
target
- Screens used to measure
the compound’s effect on
the target
- Answers question:
“How does it work?”

Question 6

Target-free (phenotypic) screening

Answer 6

Any screening which is not target based. Screens candidate drugs based on their desired effects
without knowing the mechanism of action

Targets are unknown
- Ideally use native human
cells
- Activity in phenotypic
screening might be
translated to human disease
more effectively
- Answers question:
“Does it work?”

Question 7

pros of Target based

Answer 7

Target is known
- Mechanism of action is known
- High throughput screening
- Measure compound
characteristics

Question 8

cons of target based

Answer 8

• Unsure if will translate from in
  vitro to in vivo assays
• Can’t measure compound
  properties (toxicity, off-target
  effects)

Question 9

pros of Target-free

Answer 9

Based on desired phenotype
- Uses native human cell lines
- Simultaneously measure
compound properties
- More physiologically relevant

Question 10

cons of target-free

Answer 10

• Target is unknown
• Low throughput screening
• Need identify the mechanism
  of action

Question 11

Target based assays

Answer 11

• Protein-protein interactions
• Enzyme activity

Question 12

Target-free assays

Answer 12

• Cell proliferation (growth/death)
• Reporter genes (expression)

Target based & target-free strategies are not
mutually exclusive! Can be used in combination

Question 13

High throughput screening (HTS)

Answer 13

To accelerate drug discovery by screening large compound libraries against specific targets, at a rate of over a few thousand compounds per day

Question 14

Key considerations in assay development

Answer 14

1) Relevance
2) Reproducibility
3) Robustness
4) Feasibility
5) Automation

Question 14

Hit

Answer 14

A compound which has the desired activity in a compound screen, & whose activity is confirmed upon retesting

Question 14

Confirmatory testing

Answer 14

Compounds are retested using the same assay conditions to
make sure that the activity is reproducible

Question 15

Lead Optimization

Answer 15

Following confirmation of a hit, aims to improve the lead compound by chemical modification of the lead structure to create new analogs with better effects

Question 15

Secondary screen

Answer 15

Confirmed hits are tested
in a functional cellular assay to determine
efficacy

Question 16

Pre-clinical Safety Studies

Answer 16

Focus on safety, tolerability, and efficacy of the drug. Can be performed in cell culture and/or animal models to ensure patient
safety

Question 17

Clinical trials

Answer 17

Studies to find out whether the drug is safe & effective for people

Question 18

Phase I clinical trials

Answer 18

Test an experimental drug on a small group of healthy people (20-100) for the first time

Question 19

Phase II clinical trials

Answer 19

The drug is given to a larger group of people (usually
100+) with the disease to

Question 20

Phase III clinical trials

Answer 20

The drug is given to even larger groups of people (1,000+) with the disease to

Question 21

Phase IV clinical trials

Answer 21

These trials are done after the drug is approved and is on the market. They gather information
on things like the best way to use a drug, and the long-term benefits and risks

Question 22

New Drug Submission

Answer 22

If clinical trial studies prove that the drug has potential therapeutic value that outweighs the risks, sponsor can file a NDS to the Health Products and Food Branch (HPFB) of Health Canada

Question 23

What if a drug is not approved?

Answer 23

HPFB ( Health Products and
Food Branch) will not grant a
marketing authorization for the drug