Drug Design

Question 1

How do forward and reverse genetics differ?

Answer 1

Forward = look at changes in organism when submit to one small molecule from library, then identify target.

Reverse - Start with target - look for change in animal.

Question 2

What is the rationale behind fragment based screening?

Answer 2

Complete molecules have low probability of STRONG binding.

Fragments have high probability of WEAK binding.

Question 3

Outline the strategies employed to optimize the lead compound.

Answer 3

Steric and electronic complementarity.
Buried hypho surface (increase entopy to make binding more favourable).
Conformational rigidity / stability. 
Chemical stability
Bioavailability. 
Pharmacokinetics
Soluble 
Synthesis.

Question 4

How does Lipinksi’s rule of 5 relate to passively absorbed oral delivery of drugs?

Answer 4

Low Mr <500
Moderate lipophilicity LogP <5
Low polarity - <5 H bond donors / <10 H bond acceptors.