Lec 2 Flashcards
Give 3 examples of drug targets
- GPCRs - enzymes - ligand/voltage gated ion channels
What is the dissociation constant and give the equation?
Kd = affinity of a protein for its ligand - in this case a drug target and the drug
Draw a graph that highlights how to work out Kd
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?
when half receptor sites filled, [R] = [RL] therefore Kd = [L]
Draw the graph that is associated with the EC values
What are EC50 and EC90 values?
- EC50 = concn of L to ellicit 50% response
- same for EC90 but for 90%
Give an example of a biological response
% of bacteria that are killed by a specific antibiotic
When we have an enzyme as our target, what is EC50 analagous to?
IC50
Give a definition for IC50
inhibitor concentration for a 50% decrease in enzymatic acitivty
Draw the graph that helps to determine IC50 at a variety of substrate concentrations
Concentration of a drug candidate is dependent on ___ and ___
[S] and Km
Using the equation below, what happens to the IC50 when Km is low and [S] is high?
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
Give the formula to determine the selectivity of a drug molecule
What are the 4 factors that determine whether a drug will reach its target, draw a diagram to aid your answer?
ADME
- Absorption
- distribution
- metabolism
- excretion
What are all of Lipinski’s 5 rules? What is their function?
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
Why do Lipinski’s rules not apply to biologics?
biologics are too big therefore administered via IV
What is the partition coefficent? How do we work it out?
- 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
