Drug Targets

Question 1

Describe the GPCR Cycle.

Answer 1

Question 2

The classification of G-Protein Families is based on ___________ .

Answer 2

G alpha subunit - Induced Effects

Question 3

Describe how to turn off the signal transduction pathway started by the GPCR.

Answer 3

GRK (GPCR Kinase), Beta-Arrestin, Protein Phosphatase

Question 4

List the different Protein Domains that are present within the Receptor Tyrosine Kinases.

Answer 4

1. Ligand-Binding Domain
2. Transmembrane Domain
3. Tyrosine Kinase Domain

Question 5

What is the purpose of Adaptor Proteins?

Answer 5

Adaptor Proteins provide means to create a sequential transduction pathway.

GEFs (SOS) are going to activate Monomeric GTPases

Question 6

List, in order, the growth factor pathways in cancer.

Answer 6

Growth Factor –> RTK –> G-Protein –> RAF –> MEK –> ERK –> Transcription Factor

Question 7

Describe the function of targeted anticancer drugs.

Answer 7

Inhibits upregulated growth factor (GF) signaling

Question 8

Ligand-Activated transcription factors that modulate gene expression are an example of ________ .

Answer 8

Nuclear Receptors

Question 9

True or False.

The effects of a nuclear receptor cannot persist after the agonist concentration has been reduced to zero.

Answer 9

FALSE

You will still have effects occuring because it takes a long time for the TFs to activate RNA Polymerase II and cause an effect!

Question 10

What are the various functions of:

1. Gs
2. Gi
3. Gq

Answer 10

1. Gs: Adenylate Cyclase Activation (Can activate SRC Tyrosine Kinase)
2. Gi: Adenylate Cyclase Inhibition (Can activate SRC Tyrosine Kinase)
3. Gq: Phospholipase C Activation

Question 11

What type of channels are involved in local anestetics (lidocaine), Antiarrhythmic Drugs (quinidine) and Druges used for treatement of epilepsy (phenytoine)?

Answer 11

Voltage-Gated Na+ Channels

Question 12

Where are L-Type Ca2+ channels located?

Answer 12

Cardiac and Smooth Muscle Cells

Question 13

Verapamil and Nifedipine are used to treat hypertension, arrhythmias, and ischemic heart disease. Which channel are they blocking in order to treat these diseases?

What is an adverse side effect of Verapamil?

Answer 13

Voltage-Gated Ca2+ Channels

Adverse Effect –> Constipation (Muscle relaxation in the gut)

Question 14

Acetylcholine and Glutatmate are examples of which type of neurotransmitter?

Answer 14

Excitatory

Question 15

GABA and Glycine are examples of which type of Neurotransmitters?

Answer 15

Inhibitory

Question 16

Where are the two main locations of Nicotinic Acetylcholine Receptors?

Answer 16

1. Skeletal Muscle - Responsible for depolarization of skeletal muscle fibers (Tubocurarine is an antognist drug used for nueromuscular blocks)
2. Neuronal Cells - Varenicline is a partial agonist drug that is used in smoking cessation

Question 17

Binding of GABA to its ion channel allows which ion to come into the cell?

Answer 17

Chlorine (hyperpolarization)

Question 18

Steroid Hormones, Thyroid Hormones, Lipid mediators (free fatty acids), and vitamins D/A are going to bind to which type of receptor?

Answer 18

Nuclear Receptors

Question 19

Growth hormone (somatotropin), EPO, Leptin, Interferons and Interleukins-2 to 10, 15 are going to bind to which receptor?

Answer 19

JAK-STAT Pathway

Question 20

IGF-1, Insulin, VEGF, EGF, NGF and PDGF are going to bind to which kind of receptor?

Answer 20

Receptor Tyrosine Kinase

Question 21

Describe the GPCR-cAMP pathway

Answer 21

Active G Protein - AC - cAMP - PKA - Phosphorylase Kinase - Glycogen Phosphorylase - Glycogen –> Glucose-1-Phosphate

Question 22

Biogenic Amines (Ach, Epi, NE, DA, Serotonin, Histamine), Peptides/Proteins, Aminoacids, Lipids, and Nucleotides all can bind to which receptor?

Answer 22

GPCR

Question 23

Which receptor is used as a target for inhalation/IV general anesthesia drugs, Ethanol and Valium?

Answer 23

GABA

Question 24

SH2 domains bind to which structure?

Answer 24

Phosphorylated Tyrosines

Question 25

SH3 binds to which structure?

Answer 25

Proline-rich Sequences

Question 26

Give an example of a Guanine Nucleotide Exchange Factor (GEF). What is its function?

Answer 26

SOS (Son of Sevenless)

Converts Ras-GDP –> Ras-GTP

Question 27

What does Digoxin Inhibit?

Answer 27

Na+/K+ ATPase

Question 28

What are the outcomes of Digoxin?

Adverse Side effects?

Answer 28

1. Increased Cardiac Contractility (decreases heart failure)
2. Bradycardia and slowed AV conductivity (due to increased vagal activity)

Side effects:

• Vomiting and Diarrhea (due to the increase GI contractility)
• Disorientation, confusion, and visual disturbances (due to enhanced neuronal activity)