Lecture 2: Drug Targets Flashcards
T or F
When a GPCR is activated the affinity of its G-protein alpha subunit for GDP is decreased
True
The receptors for a group of signaling molecules known as GFs are often:
A) Ligand-gated ion channels
B) GPCRs
C) Nuclear receptors
D) Membrane transporters
E) Receptor tyrosine kinases
E. Receptor tyrosine kinases
What are 3 targets of targeted anticancer drugs?
1) Monoclonal antibodies to GF receptors
2) Monoclonal antibodies to ligands of GF receptors
3) Multikinase inhibitors
What is inhibited by targeted anticancer drugs?
Upregulated GF signaling
Spironolactone is what type of drug?
Used to treat what?
- Aldosterone receptor antagonist
- Tx for chronic HTN and alleviates chronic heart failure
What is the MOA of the drug Verapamil?
- Blocks L-type calcium channels = Calcium antagonist
- Used to tx atrial and supraventricular arrythmia, angina pectoris, and HTN
What is an adverse effect of Verapamil?
Constipation
What is the MOA of Digoxin?
Inhibits Na+/K+-ATPase –> enhances cardiac contractility
Which pathology is Digoxin used to treat?
CHF
What do TF’s regulate the recruitment of?
Either promote (activators) or inhibit (repressors) the recruitment of RNA polymerase to specific genes
What are 5 GPCR ligands?
1) Biogenic amines
2) Peptides/proteins
3) AAs
4) Lipids
5) Nucleotides
What are the classes of GPCRs and their functions?
- Gs: activates adenylyl cyclase and Src tyrosine kinase
- Gi: inhibits adenylyl cyclase but activates Src tyrosine kinase
- Gq: activates phospholipase C
What specific DNA sequence do TF’s bind to?
Response element
What is unique about insulin and IGF RTKs?
Contain 2 polypeptide chains, α and β, linked by disulfide bond
*Most RTKs possess a single polypeptide chain
List 5 hormones/cytokines that utilize a JAK-STAT pathway for signaling?
1) GH (somatotropin)
2) Erythropoietin
3) Leptin
4) Interferons
5) IL-2 to 10, and 15
IGF-1, VEGF, EGF, NGF, and PDGF are able to assert their actions through the use of which type of receptor?
Receptors with tyrosine kinase activity (RTK)
What is the defining feature of a TF?
Presence of the DNA-binding domain
What is unique about the effects of nuclear receptor drugs?
Effects can persist after the agonist concentraton has been reduce to zero
Describe the mechanism of a steroid hormone activating its receptor?
How is the receptor inactivated?
- In absence of hormone, hsp90 is bound and prevents folding into active conformation
- Binding of a hormone ligand (steroid) dissociates hsp90 and permits conversion to active configuration
What 3 types of drugs are inhibitors of voltage-gated Na+ channels?
1) Local anesthetics
2) Antiarrythmia drugs
3) Epilepsy drugs
Activation of a Nicotinic acetylcholine receptor induces influx of?
Causes?
- Na+
- Membrane depolarization
Nicotinic acetylcholine receptors are pentameric receptor found in what 2 locations?
1) Skeletal muscle
2) Neuronal cells
What is the differene between the actions of excitatory and inhibitory NTs in terms of channels they open?
- Excitatory (ACh and Glutamate) open cation channels –> depolarization –> APs
- Inhibitory (GABA and Glycine) open anion channels –> hyperpolarization –> prevent APs
GABA-A receptors are what type of channels and cause the influx of what?
Affects membrane potential how?
Anionic channels causing inward Cl- influx and hyperpolarization
