Konorev Drug Targets

Question 1

what is a component of the biologic system to which a drug binds without changin any function

Answer 1

inert binding site

Question 2

what contains a variety of protein binding domains that link protein partners together and facilitate the creation of larger signaling complexes

Answer 2

adaptor proteins

Question 3

what are the major classes of drug targets

Answer 3

membrane receptors
nuclear receptors
ion channels
transport proteins
enzymes

Question 4

what is the defining feature of a txn factor

Answer 4

presence of DNA-binding domain

Question 5

where do txn factors usually bind

Answer 5

to enhancer or promoter regions of DNA that are usually adjacent to the coding sequence of the redulated gene
called response element

Question 6

GPCR: biogenic amines ligands

Answer 6

DANESH
mean danesh

dopamine
acetylcholine
norepineprhine
epineprhrine
serotonin 
histamine

Question 7

GPCR peptides/proteins ligands

Answer 7

A BOA

ACTH
bradykinin
opioids
angiotensin

Question 8

gpcr ligands aminoacids

Answer 8

glutamate

gaba

Question 9

gpcr ligands: lipids

Answer 9

LTP fat
lawrence taylors penis is fat

leukotrienes
thromboxane A2
prostacyclin

Question 10

gpcr ligands: nucleotides

Answer 10

adeonsine
adp
atp

Question 11

strucutre of GPCR

Answer 11

7 transmembrane domains
N terminal (extracellular) often glycosylated
C-terminal (cytosolic) contains multiple phosphorylation sites (ser/thr residues)

Question 12

Gs familhy

Answer 12

activates all isoforms of adenylyl cyclase and src tyrosine kinase

Question 13

Gi family

Answer 13

inhibits adenylyl cyclases but activates tyr kinase Src

Question 14

Gq family

Answer 14

activates phospholipase CB

Question 15

desensitization process

Answer 15

agonist binding to receptors initiates signaling by promoting receptor interaction with Gs proteins
-agonist activated receptors are phosphorylated by GRK which prevents interaction with Gs and B-Arr binds

• receptor-arrestin complex binds to coated pits, which promots internalization
• dissociation of agonist from internalized receptors reduces B-arr binding and allows dephos of receptors by phosphatase, receptors return to PM
• repeated or prolonged exposure of cells to agonist favors delivery of internalized receptors to lysosomes = down reg over resensitization

Question 16

receptors with intrinsic enzyme activity

Answer 16

Receptor tyrosine kinases (VIN PIE)

VEGF
IGF-1
NGF
PDGF
Insulin
EGF

Question 17

which of the receptor tyrosine kinsases have 2 chains and exist as dimers in resting state

Answer 17

IGF-1 and insulin

Question 18

what converts RAS-GDP to RAS-GTP

Answer 18

GEF

-SOS

Question 19

pt mutation in RAS found in 90% of

Answer 19

pancreatic cancer

Question 20

pt mutation in Raf found in 70% of

Answer 20

melanomas

Question 21

targeted anticancer drugs inhibit upregulated GF signaling how

Answer 21

monoclonal Abs to GF receptors and their ligans

-also mutlikinase inhibitors

Question 22

examples of receptors coupled to cytosolic protein kinases

-hormones and cytokines involved

Answer 22

JAK-STAT

GH (somatotropin)
erythropoetin
leptin
interleukin 2,10,15
interferons

(GELII)

Question 23

jak stat path

Answer 23

cytokine receptors activated then JAK activated which phosphorylates STAT which forms a dimer and heads to the nucleus

Question 24

liphophilic ligands

Answer 24

steroids
thyroid hormones
vitamin D, vit A
lipid mediators like free FAs

Question 25

steroid receptor family

Answer 25

mineralocorticoid receptors
progesterone receptors
androgen receptors
glucocorticoid receptors
estrogen receptors

-produce effect after a lag period, several hours to days
-effects can persist after agonist conentration has been reduced to 0
-

Question 26

mechanism of steroid hormone action

Answer 26

has hsp90 binding recepotr in absence of hormone to prevent folding into active conformation of receptor

binding of ligand causes dissociation of hsp90 and permits conversion to active configuration

Question 27

which subunit is responsible for the ion pore in voltage gated sodium channels

Answer 27

alpha

Question 28

inhibitors of voltage gated sodium channels

Answer 28

local anesthetics
antiarrhythmic drugs
drugs used for treatment of epilepsy

Question 29

voltage gated calcium channels targets of drugs for use of

Answer 29

hypertension, arrhythmias, ischemic herat disease