Drug Targets - 8/1 Konorev

Question 1

What are the GPCR ligands?

Answer 1

Biogenic amines (nt's)
Peptides/proteins
Aminoacids (Glu, GABA)
Lipids
Nucleotides (ATP)

Question 2

What does the Gi family inhibit?

Activates what?

Answer 2

Adenylyl cyclase

Tyr Kinase SRC

Question 3

Gq activates what?

Answer 3

PLC

Question 4

Starting with PLC, describe the downstream pathways:

Answer 4

PLC -> PIP2 -> IP3 -> CaM

PLC -> PIP2 -> DAG -> PKC

Question 5

Name the diff type of RTKs

Answer 5

GFs like IGF, VEGF, EGF, NGF, PDGF

And insulin

Question 6

Insulin is a type of what?

What special structural features does it have?

Answer 6

RTK

2 chains alpha and beta linked by a DSB

Question 7

Ras is considered what?

Answer 7

Monomeric GTPase

Question 8

SH2 domains bind what?

Answer 8

Tyrosines

2 Ty

Question 9

SH3 domains bind what?

Answer 9

Proline-rich sequences

Question 10

GEFs activate what?

Example of 1

Answer 10

Monomeric GTPases

Sos

Question 11

what inactivate monomeric GTPases?

How?

Answer 11

GAPs

GTP hydrolysis

Question 12

What mutation is found in 70% of melanomas?

Answer 12

point mutation in Raf

Question 13

What mutation is found in 90% of pancreatic adenocarcinomas?

Answer 13

Point mutation in Ras

Question 14

Give the signal transduction starting with a GF down to protein expression

Answer 14

GF -> RTK -> G-protein -> Raf -> MEK -> ERK -> to nucleus for transcription -> protein expression

Question 15

What activates the JAK receptors?

Answer 15

GH (somatotropin)
EPO
Leptin
IFN
IL-2 to 10, 15

Question 16

JAK inhibitors are used in what disorders?

Answer 16

Allergic and autoimmune

Question 17

What are nuclear receptors?

Answer 17

Steroid and thyroid hormones
Vit D, Vit A
Lipid mediators (FFA)
Steroid receptor

Question 18

How long is the lag period for nuclear receptors?

Answer 18

Hours to days

Question 19

What prevents folding into the active conformation of the receptor in the absence of a hormone?

Answer 19

Hsp90

Question 20

What drug is used to treat osteoporosis in menopausal women and breast cancer?

Answer 20

Tamoxifen

Question 21

What is a nuclear receptor antagonist drug?

Answer 21

Spironolactone

Question 22

What is an analog of endogenous ligands as agonists?

Answer 22

Levothyroxine

Question 23

Conductance is induced my membrane potential changes describes what?

Answer 23

VG-channels

Question 24

What channels play a role in changing the cell membrane potential?

What else do they do?

Answer 24

Ion channels

Change the [ ] of ions in cytosol

Question 25

What channels are multimedia and span the cell membrane and have a binding site for a nt inducing the current and an ion-conducting pore?

Answer 25

Ligand-gated

Question 26

What are VG channels controlled by? Do they bind nts directly?

Answer 26

Membrane potential NO

Question 27

What composes VG-Na channels?

Answer 27

Alpha and beta subunits

Question 28

Where are L-type Ca channels located? What type are they?

Answer 28

Cardiac and smooth m. VG

Question 29

What do excitatory nts do? Examples?

Answer 29

Open cation channels, depolarize the cell and generate AP ACh Glutamate

Question 30

What do inhibitory nts do? Examples?

Answer 30

Open anion channel causing hyperpolarization, prevent APs GABA Glycine

Question 31

Activation of Nicotinic ACh receptors causes what? Located where? What structure?

Answer 31

Inward Na+ flux and membrane depolarization Skeletal m. And neuronal cells Pentameric (2a, 1b, 1 gamma, 1 delta)

Question 32

The Nicotinic ACh receptor is what?

Answer 32

Ligand-gate ion channel

Question 33

Where does ACh bind to the Nicotinic receptor?

Answer 33

Alpha subunit

Question 34

GABA receptor activation causes an inward flux in what ion? Mediates what, where?

Answer 34

Cl- Synaptic inhibition in CNS

Question 35

What structure of GABA receptor?

Answer 35

Pentameric

Question 36

Examples of GABA drugs?

Answer 36

Halothane Proposal Valium

Question 37

What are examples of peptides/proteins?

Answer 37

ACTH Angiotensin Bradykinin Opioids

Question 38

What are examples of Lipids?

Answer 38

LTKs Prostacyclin TxA2

Question 39

What are the Biogenic amines?

Answer 39

``` ACh Epi NE Dopamine Serotonin Histamine ```