Drug targets-Konorev

Question 1

The general name for an enzyme that transfers phosphate groups from ATP to a protein is __

Answer 1

Protein kinase

• Ser-Thr kinases
• Tyr kinases

Question 2

The specific DNA sequence a TF binds to is called a ___

Answer 2

Response element

Question 3

___ activates all isoforms of adenylyl cyclas and Src tyrosine kinase

Answer 3

Gs

Question 4

__ inhibits AC but activates tyrosine kinase Src

Answer 4

Gi

Question 5

___ activates PLC

Answer 5

Gq

Question 6

List the steps in the GPCR-cAMP signaling cascade

Answer 6

Ligand binds receptor –> Gs activation (active G protein) –> Activate AC –> ATP to cAMP –> Activate PKA –> Activate Phosphorylase kinase –> Activate glycogen phosphorylase

Question 7

DAG is a lipophilic intermediate that activates ___

Answer 7

Protein Kinase C

Question 8

List the steps in the DAG and IP3 pathway:

Answer 8

Ligand binds receptor –> Activate G protein –> Activate PLC –> PIP2 activates DAG and IP3

• DAG –> PKC
• IP3 –> Releases Ca –> Ca-CaM complex

Question 9

The receptors for a group of signaling molecules known as growth factors are often ___

Answer 9

Receptor tyrosine kinases

Question 10

Receptors with RTK transmit the action of a number of ___

Answer 10

growth factors

-IGF-1, insulin, EGF, NGF, PDGF

Question 11

the __ domain of an RTK shows very little similarity between members of the family

the __ domain of an RTK is similar between members of the family

Answer 11

ligand-binding

tyrosine kinase

Question 12

proteins that contain a SRC homology 2 domain (SH2 domain) bind to proteins that have a ___ residue

Answer 12

phosphotyrosyl

Question 13

___ domain binds to the phosphorylated tyrosines

__ domain binds to the proline-rich sequences

Answer 13

SH2

SH3

Question 14

A ras protein is known as a __ GTPase

Answer 14

monomeric

Question 15

list the components of the activation of a monomeric GTPase Ras by growth factors:

GF receptor: ___
Adaptor protein: ___
GEFs: ___
Monomeric GTPase protein: ___

Answer 15

RTK

Grb2

SOS

Ras

Question 16

Point mutations in __ found in 90% of pancreatic adenocarcinomas

Point mutations in __ found in 70% of melanomas

Answer 16

Ras

Raf

Question 17

binding of a NT to this type of receptor directly leads to a change in distribution of ions between extra and IC compartments

Answer 17

Ligand-gated ion channel

Question 18

__ channels are multimeric channels that span the cell membrane and have a binding site for a NT inducing the current, and an ion-conducting pore

Answer 18

Ligand-gated

Question 19

Excitatory NTs open __ channels, depolarize the cell and induce generation of AP in excitable cells

Answer 19

cation

Question 20

Inhibitory NTs open __ channels causing inward flux and hyperpolarization, preventing generation of APs

Answer 20

anion

Question 21

permeability to what ion is increased a result of the activation of a nicotinic receptor?

Answer 21

Mostly Na

Question 22

Nicotinic Ach receptors are generally found where?

Answer 22

neuronal and skeletal m. cells

Question 23

binding of GABA to its cognate receptor ion channel will cause influx of __

Answer 23

mostly Cl

Question 24

Transcription factors promote or inhibit the recruitment of ___ to specific genes

What is the defining feature of Transcription factors?

Answer 24

RNA polymerase

DNA-binding domain

Question 25

Transcription factors bind to ___regions of DNA that are usually adjacent to the ___ sequence of the regulated gene. The specific DNA sequence they bind to is called the ___

Answer 25

Enhancer or promoter Coding Response element

Question 26

G-protein binding sites are located where?

Answer 26

Cytosol

Question 27

In the DAG and IP3 pathway, what activates these 2?

Answer 27

Phosphatidylinositol disphosphate (PIP2)

Question 28

What activates monomeric GTPases?

Answer 28

GEFs

Question 29

What inactivates monomeric GTPases by accelerating GTP hydrolysis?

Answer 29

GAPs

Question 30

Point mutations in __ are found in 90% of pancreatic adenocarcinomas

Answer 30

Ras

Question 31

Point mutations in ___ are found in 70% of melanomas

Answer 31

Raf

Question 32

What are examples of the types of drugs that inhibit GF signaling in carcinogenesis?

Answer 32

Monoclonal antibodies to GF receptors and their ligands Multikinase inhibitors

Question 33

JAK is found in which part of the cell?

Answer 33

Cytosol

Question 34

Recombinant ligans (HGH, EPO, IFN, and IL-2), receptor antagonists such as pegvisomant (a GH antagonist), and drugs used in allergic and autoimmune disorders target the __ pathway

Answer 34

JAK-STAT

Question 35

List some ligands that target nuclear nuclear receptors:

Answer 35

Steroids, thyroid hormones, Vit A and D, lipid mediators such as free FAs and their products

Question 36

In the mechanism of a steroid hormone action, binding of a hormone ligand (steroid) causes dissociation of what?

Answer 36

hsp90 Binding of steroid causes dissociation of the hsp90 stabilizer and permits conversion to the active configuration

Question 37

___ channel conductance is induced by membrane potential changes and Na, Ca, and K channels are targets of drug action

Answer 37

Voltage-gated

Question 38

__ channels are multimeric channels that span the cell membrane and have a binding site for a NT inducing the current, and an ion-conducting pore

Answer 38

Ligand-gated

Question 39

__ do not bind NTs directly but are controlled by membrane potential

Answer 39

Voltage-gated

Question 40

Local anesthetics (lidocaine), antiarrhythmic drugs (quinidine), and drugs used for tx of epilepsy (phenytoine) act to inhibit __

Answer 40

Voltage-gated Na channels

Question 41

__ channels are located on cardiac and smooth muscle cells

Answer 41

L-type voltage-gated Ca channels

Question 42

__ are receptors for NTs that have an ion-conducting pore

Answer 42

Direct ligand-gated ion channels

Question 43

___ open cation channels, depolarize the cell and induce generation of AP in excitable cells

Answer 43

Excitatory NTs

Question 44

List examples of Excitatory NTs

Answer 44

Ach and glutamate

Question 45

___ open anion channels causing inward anion flux and hyperpolarization, preventing generation of APs

Answer 45

Inhibitory NTs

Question 46

List examples of inhibitory NTs

Answer 46

Gaba and glycine

Question 47

Activation of a nicotinic Ach receptor induces inward ___ fluxes and membrane depolarization

Answer 47

Na

Question 48

Antagonist drugs used as neuromuscular blockers (Tubocurarine) and partial agonist drugs used for smoking cessation (Verenicline) are examples of this pentameric receptor:

Answer 48

Nicotinic Ach receptor

Question 49

GABA-A receptors are anionic channels that cause inward __ influx and hyperpolarization. GABA mediates synaptic inhibition in CNS via these channels

Answer 49

Cl

Question 50

This type of receptor is a target for: - inhalation general anesthesia drugs (halothane) - IV general anesthesia drugs (propofol) - ethanol - hypnotic and anti-anxiety benzodiazepine drugs (valium)

Answer 50

GABA-A

Question 51

Volatile anesthetics and ethanol target the ___ subunit of the GABA-A receptor Neurosteroids and propofol target the __ subunit of the GABA-A receptor

Answer 51

Alpha Beta

Question 52

Cardiac glycosides target the ___

Answer 52

Na pump

Question 53

Thiazide diuretics (chlorothiazide) target the __

Answer 53

Na/Cl co-transporter

Question 54

Loop diuretics target the ___

Answer 54

Na/K/Cl co-transporter

Question 55

Adrenergic drugs (reserpine) target ___

Answer 55

VMAT

Question 56

Adrenomimetic drugs (ephedrine, amphetamines) target __

Answer 56

NE transporter

Question 57

Antidepressants (paroxetine) target )))

Answer 57

SERT (serotonin/Na symporter)