Drug target pt2

Question 1

Drug targets can be divided into 2 groups.

Answer 1

•Phenotypic screening–“Classical pharmacology”
–Animal models or clinical observations of secondary effects provide the leads
–Library of chemical analogs are tested in animal models to optimize structure/activity (QSAR)
–Iterative optimization process

•Target-based drug discovery–“Reverse pharmacology”
–Genetic finds and molecular biology provides leads
–Protein modeling can assist drug design–In vitro experiments preceedes animal data
–Optmization in vitro

Question 2

What does drug target act on

Answer 2

Receptors, enzymes, transporters and ligands

Question 3

Which are the receptor drug targets?

Answer 3

–G protein-coupled receptors (GPCRs)
•The largest protein family in approved drug targets

–Enzyme-coupled receptors
•Receptor tyrosine kinases (RTKs) –These are also enzymes
•Cytokine receptors

–Ligand-gated ion channels –These are also transporters
–Nuclear receptors

Question 4

Receptor type protein kinases (RTKs)

Answer 4

Examples–Insulin R–IGF Type 1 R–EGFR–VEGFR–PDGFR
Transfers a phosphate group from ATP to a target protein tyrosine moiety
•Essential for signal transduction mediating growth, proliferation, differentiation, cell cycle regulation

Question 5

G Protein-coupled Receptors, (GPCRs)

Answer 5

Specified function and expression give the potential for high specificity with low side effects
•Signaling cascades generate large effects from low ligand concentrations
•Enormous range of function and indications–Cancer, pain management, hypertension, schizophrenia, diabetes, allergy, depression, constipation, sleep disorders, inducing labor, etc. etc.