Drugs Targets- Catalytic & Nuclear receptors

Question 1

Structure of catalytic receptor

Answer 1

• Has extrecellular binding site (N terminal) ligand bind
• Intracellular enzyme domin in receptor (C-terminal)
• Ligands are peptides or protiens

Question 2

Dimerization

Answer 2

• Leads to activation as 2 subunits
• Ligand binds to binding site to form one receptor complex (dimer)
• Autophosphorylation occours in the transmembrane which transforms throught the catalytic intracellular domain

Question 3

Catalytic receptors example

Answer 3

• Tyrosine kinase receptor
• Guanylyl cyclase receptor

Question 4

peptides that activate receptor tyrosine kinase

Answer 4

• Receptor for growth factors
• Insulin
• Neurotrophin
• Epidemal growth factor

Question 5

What occours as a result of the activation of protien kinase

Answer 5

• Cell proliferation
• Cell differentiation
• Survival and metabolism

Question 6

Hyperactivation of receptor tyrosine kinase

Answer 6

• Polyps
• Tumour and cancer

Question 7

Process of tyrosine kinase activation

Answer 7

• Growth factor binds to RTK leading to dimerization and autophosphorylation
• Once activating the autophosphorylation intracellular causing the recruitment of signalling protiens

Question 8

What does a signalling protien contain

Answer 8

• SH2 domain senses specific and bind to specific RTK

Question 9

Enzymes that are SH2 domain protiens

Answer 9

• Directly produce signals e.g. phospholipase C leads to the activation of intracellular calcium release and protien kinase C activation

Question 10

SH2 protiensthat are adaptors

Answer 10

• Link RTKs to signalling protiens
• Grb2 links the EGF receptor and SOS which is a regulator of Ras-MAP kinase

Question 11

Insulin drug RTKs

Answer 11

• Life saving drug that stimulates RTK for diabetes patients

Question 12

Avastin

Answer 12

• Blocks the tumour by antigiogenesis new blood vessel formation VEGF
• Use antibody to target the growth factor blocking binding

Question 13

Herceptin

Answer 13

• Targets overly expressed oestrogen receptor for breast cancer

Question 14

Guanylyl cyclase receptor

Answer 14

• Limited membrane bound receptor
• Aterial natiuretic peptide
• Released from atria promoting vasodialation and sodium extreation urine

Question 15

GTP activation

Answer 15

• GTP is activated by RTK Guanynyal converting to cyclic GMP
• Activation of protien kinase G then vasodialation

Question 16

Cytoplasmic Guanynyal cyclase receptor

Answer 16

• Nitric oxide which is an endothelium derived vasodialator factor which stimulates Guanynal cyclase
• Elevate intracellular cGMP
• Activation of protien kinase G and smooth muscle relaxation
• PDE isoform breaks down cGMP

Question 17

Sidenafil

Answer 17

• Inhibition of PDE

Question 18

Cytoplasmic and nuclear receptor

Answer 18

• Intracellur receptor and transcripton factor binding occours

Question 19

Cytoplasmic receptor activation

Answer 19

• Steroid hormone can target the cytoplasmic receptor due to lipophilicity can diffuse into plasma membrane
• Oestrogen activation of breast tissue

Question 20

Tamoxifen

Answer 20

• Acts on the specific oestrogen dependant receptor
• Antagogise the oestrogen binding

Question 21

Nuclear receptor

Answer 21

• Diffuse through the ligand and activate cytoplasmic transcriptoin factor
• Migrate to the nucleus where it is responsible for synthesis of new protien