Drug Targets

Question 1

What is a drug target?

Answer 1

A molecular target that illicits a biological response

Question 2

Give examples of drug targets

Answer 2

Enzymes
Receptors
Transporters
Ion channels
Nucleic acids
Nuclear receptors
GPCRs

Question 3

What is an agonist for a GPCR?

Answer 3

A molecule that triggers a G protein cycle

Question 4

Describe a G protein cycle

Answer 4

GDP is exchanged for GTP
The heterotrimer is broken up into an alpha and beta gamma subunit
The beta gamma subunit stimulates a signal cascade
The alpha subunit binds to GDP to inactivate the G-protein and reform the heterotrimer

Question 5

How can protein structures be determined

Answer 5

X-ray crystallography

Purification -> Crystallisation -> X-ray -> image taken on film

Question 6

Describe the target of salbutamol

Answer 6

Beta-2 adrenoreceptors

Binds in the middle of the transmembranal helices and activates resulting in bronchiole dilation

Question 7

Describe the target of candasartan

Answer 7

Angiotensin T1 receptors

Binds in the middle of the transmembranal helices and inhibits angiotensin binding to reduce blood pressure

Question 8

Describe the target of methotrexate

Answer 8

Binds to dihydrofolate reductase
Prevents reduction of dihydrofolic acid which kills rapidly dividing cells as it’s needed to make purines and pyrimidines

Question 9

Describe the target of trimethoprim

Answer 9

Binds to dihydrofolate reductase in bacteria to prevent bacterial replication

Question 10

Describe the target of saquinavir

Answer 10

Targets HIV protease to inhibit viral proliferation. Recognised by proteases but will not be cleaved`

Question 11

Describe the target of ibuprofen/aspirin

Answer 11

Inhibition of cyclooxygenase so inflammatory mediators are not produced

Question 12

Describe the target of neostigmine

Answer 12

Binds to acetylcholine esterase to prevent the breakdown of acetylcholine at the neuromuscular junction

Question 13

Describe the target of fluoxetine/sertraline

Answer 13

Blocks serotonin transporters to prevent serotonin reuptake

Question 14

Describe the target of cocaine

Answer 14

Blocks dopamine transporters to prevent dopamine reuptake

Question 15

Describe the target of forxiga

Answer 15

Blocks sodium dependent glucose transporters in the kidneys to prevent glucose reabsorption and reduce blood sugar, independent of insulin

Question 16

Describe the target of sulphonylureas

Answer 16

Targets ATP sensitive potassium ion channels to block them and cause depolarisation of beta cells. This depolarisation opens calcium ion channels which stimulates the exocytosis of insulin

Question 17

Describe the target of diazepam

Answer 17

Targets chloride ion ligand gated channel (GABA). Diazepam inhibits the GABA channel

Question 18

Describe the target of actinomysin

Answer 18

Intercalates between DNA bases to prevent replication

Question 19

Describe the target of tamoxifen

Answer 19

Undergoes phase 1 metabolism to become endoxifen which then binds to oestrogen receptors