Lec 2

Question 1

Give 3 examples of drug targets

Answer 1

• GPCRs - enzymes - ligand/voltage gated ion channels

Question 2

What is the dissociation constant and give the equation?

Answer 2

Kd = affinity of a protein for its ligand - in this case a drug target and the drug

Question 3

Draw a graph that highlights how to work out Kd

Answer 3

Question 4

When happens, in terms of the [R]/[RL] concentrations when half of the receptor sites are filled? What does this mean for the Kd equation?

Answer 4

when half receptor sites filled, [R] = [RL] therefore Kd = [L]

Question 5

Draw the graph that is associated with the EC values

Answer 5

Question 6

What are EC50 and EC90 values?

Answer 6

• EC50 = concn of L to ellicit 50% response
• same for EC90 but for 90%

Question 7

Give an example of a biological response

Answer 7

% of bacteria that are killed by a specific antibiotic

Question 8

When we have an enzyme as our target, what is EC50 analagous to?

Answer 8

IC50

Question 9

Give a definition for IC50

Answer 9

inhibitor concentration for a 50% decrease in enzymatic acitivty

Question 10

Draw the graph that helps to determine IC50 at a variety of substrate concentrations

Answer 10

Question 11

Concentration of a drug candidate is dependent on ___ and ___

Answer 11

[S] and Km

Question 12

Using the equation below, what happens to the IC50 when Km is low and [S] is high?

Answer 12

IC50 = Ki * large no.

IC50 will be high due to the high concn of substrate and the high affinity of the receptor/target to the natural substrate

Question 13

Give the formula to determine the selectivity of a drug molecule

Answer 13

Question 14

What are the 4 factors that determine whether a drug will reach its target, draw a diagram to aid your answer?

Answer 14

ADME

• Absorption
• distribution
• metabolism
• excretion

Question 15

What are all of Lipinski’s 5 rules? What is their function?

Answer 15

Poor absorption of a drug is likely when…

• MW > 500
• No. H bond donors > 5
• No. H bond acceptors > 10
• Partition coefficent (log(P)) > 5
• 5th rule = sum of all of above rules

Question 16

Why do Lipinski’s rules not apply to biologics?

Answer 16

biologics are too big therefore administered via IV

Question 17

What is the partition coefficent? How do we work it out?

Answer 17

• describes the tendency of a molecule to dissolve in a membrane and therefore pass into the cell
• correlates to its ability to dissolve in an organic solvent

log(P) = log ( [ligand (solvent)] / [ligand (aq)]

• if a molecule is too hydrophobic then it will be able to pass through the membrane easily but wont be able to dissolve @ its surface