Lecture 1 Target Selection and Lead Identification

Question 1

How to develop a new drug?

Answer 1

Slide 3

Question 2

What are the different types of drugs to develop/Reason to develop drugs?

Answer 2

Slide 4

Question 3

What are the steps to developing a drug?

Answer 3

Slide 5 (similar to slide 3)

Question 4

What is the traditional approach of target selection?

Answer 4

Slide 6

Question 5

What are the different approaches to identify targets? (with egs)

Answer 5

• Slide 7 (Genomic approach) + Slide 8 (BCR-Abl)
• Slide 9 (Proteomics approach) + Slide 10 (Steps for proteomics)
• Slide 11 (How to perform genomic + proteomic approach)

Question 6

How to verify that the protein/gene is really targetable + Eg?

Answer 6

Slide 12 and 13 (using example)

Question 7

How to validate your target after selection/verification?

Answer 7

Slide 14, 15, 16

Question 8

What does HIT, LEAD and Preclinical Development Candidate mean?

Answer 8

Slide 18

Question 9

What are the 2 ways of lead identification?

Answer 9

Slide 19

Question 10

How is rational drug design done + eg?

Answer 10

Slide 20, 21, 22

Question 11

What is HTS and how is it done?

Answer 11

Slide 24, 25,26, 27, 28

Question 12

How do you determine the quality of HTS assay?

Answer 12

• Robust screening assay; measure the quality of assay used to quantify
  Slide 29

Question 13

What are the adv and disadv of rational drug design and HTS?

Answer 13

Slide 31

Question 14

What is an alternative method for lead identification?

Answer 14

Slide 32, 33

Question 15

What characteristics should a common library (of drugs) have?

Answer 15

Slide 34, 35

Question 16

What is the Lipinski Rule of 5?

Answer 16

Slide 36, 37

Question 17

How do you decide which HIT becomes the LEAD?

Answer 17

Slide 38

Question 18

How do you identify a target?

Answer 18

• Proteomics
• Genomics

Question 19

What is critical to target validation?

Answer 19

LOF, GOF

Question 20

HIT/LEAD identification - Rational drug design vs HTS
What does that mean?

Answer 20

• Rational drug design: Knowing the structure and designing based on it
• HTS: Testing all the drugs to see which one is a hit for the target molecule at given concentration and lowest toxicity

Question 21

What is a good primary assay (both in concept and by Z’ score?)

Answer 21

• Relevant, sensitive in measuring the efficacy of binding to the target protein
• Z score formula