receptors and drug targets

Question 1

Describe and give examples of the four main classes of proteins targeted by drugs in mammalian cells.

Answer 1

• receptors
  
  • e.g morphine and humira
• channels
  
  • e.g lidocaine and valium
• enzymes
  
  • e.g viagra and aspirin
• transporters
  
  • e.g prozac and digoxin

Question 2

Describe canonical signalling mechanisms used by ionotropic receptors commonly targeted by drugs to bring about changes in cell function.

Answer 2

ionotropic
- charged molecules moving electric current through aqueous pore, changing potential of membrane
- e.g P2X-3P = ATP, glutamate-4P = glutamate

Question 3

Describe canonical signalling mechanisms used by GPCR receptors commonly targeted by drugs to bring about changes in cell function.

Answer 3

1. agonist binds → rearrangement of protein
2. activates G protein
3. GTP replaces GDP and a separates from by = unattractive
4. aGTP (nuclear kinase) → downstream effector proteins and GTP is hydrolysed back to GDP + Pi
5. a rejoins by and cycle repeats

Question 4

Describe canonical signalling mechanisms used by kinase receptors commonly targeted by drugs to bring about changes in cell function.

Answer 4

• enzyme linked
• regulate inflammatory responses
• growth factors - phosphorylation cascades
• can change transcription

Question 5

Describe canonical signalling mechanisms used by nuclear receptors commonly targeted by drugs to bring about changes in cell function.

Answer 5

class I - in cytosol, moves in when agonist is bound = homodimer

class II - in nucleus = heterodimer

• directly bind to and regulate transcription of genes

Question 6

Define drugs classed as ‘biopharmaceuticals’ and describe how these differ from conventional small molecule drugs.

Answer 6

→ differ in size
→ molecules are chemically prepared, biopharm are extracted
e.g
- proteins e.g insulin/antibodies
- oligonucleotides → protein production
- gene therapy
- regenerative medicine

Question 7

3 types of opioid receptors

Answer 7

mu, delta, and kappa
- mute = strongest affinity
- heroine, codeine, fentanyl bind here

Question 8

define drug

Answer 8

A chemical (of known structure) which when administered to a living organism produces a biological effect

Question 9

define medicine

Answer 9

A chemical preparation that usually contains one or more drugs administered to produce a therapeutic effect

Question 10

what are biopharmaceuticals?

Answer 10

is any pharmaceutical drug product manufactured in, extracted from, or semi synthesized from biological sources

Question 11

difference between inverse agonist, agonist and antagonist

Answer 11

inverse = reduce signalling of that receptor
agonist = stimulate receptor
antagonist = blocks receptor

Question 12

difference between blockers and modulators

Answer 12

permeation blocked vs increased/decreased opening probability

Question 13

false substrate

Answer 13

abnormal metabolite produced at end of enzymatic reaction

Question 14

prodrug

Answer 14

active drug produced at end of enzymatic reaction

Question 15

what and how does colchichine target?

Answer 15

• used for gout
  
  • targets microtubules (cytoskeleton) and prevents assembly in cells at sites of inflammation

Question 16

what and how does paclitaxel target?

Answer 16

• interferes with microtubules (cytoskeleton) and prevents disassembly and prevents cell division - chemotherapy