Konorev Drug Targets Flashcards
what is a component of the biologic system to which a drug binds without changin any function
inert binding site
what contains a variety of protein binding domains that link protein partners together and facilitate the creation of larger signaling complexes
adaptor proteins
what are the major classes of drug targets
membrane receptors nuclear receptors ion channels transport proteins enzymes
what is the defining feature of a txn factor
presence of DNA-binding domain
where do txn factors usually bind
to enhancer or promoter regions of DNA that are usually adjacent to the coding sequence of the redulated gene
called response element
GPCR: biogenic amines ligands
DANESH
mean danesh
dopamine acetylcholine norepineprhine epineprhrine serotonin histamine
GPCR peptides/proteins ligands
A BOA
ACTH
bradykinin
opioids
angiotensin
gpcr ligands aminoacids
glutamate
gaba
gpcr ligands: lipids
LTP fat
lawrence taylors penis is fat
leukotrienes
thromboxane A2
prostacyclin
gpcr ligands: nucleotides
adeonsine
adp
atp
strucutre of GPCR
7 transmembrane domains N terminal (extracellular) often glycosylated C-terminal (cytosolic) contains multiple phosphorylation sites (ser/thr residues)
Gs familhy
activates all isoforms of adenylyl cyclase and src tyrosine kinase
Gi family
inhibits adenylyl cyclases but activates tyr kinase Src
Gq family
activates phospholipase CB
desensitization process
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
receptors with intrinsic enzyme activity
Receptor tyrosine kinases (VIN PIE)
VEGF IGF-1 NGF PDGF Insulin EGF
which of the receptor tyrosine kinsases have 2 chains and exist as dimers in resting state
IGF-1 and insulin
what converts RAS-GDP to RAS-GTP
GEF
-SOS
pt mutation in RAS found in 90% of
pancreatic cancer
pt mutation in Raf found in 70% of
melanomas
targeted anticancer drugs inhibit upregulated GF signaling how
monoclonal Abs to GF receptors and their ligans
-also mutlikinase inhibitors
examples of receptors coupled to cytosolic protein kinases
-hormones and cytokines involved
JAK-STAT
GH (somatotropin) erythropoetin leptin interleukin 2,10,15 interferons
(GELII)
jak stat path
cytokine receptors activated then JAK activated which phosphorylates STAT which forms a dimer and heads to the nucleus
liphophilic ligands
steroids
thyroid hormones
vitamin D, vit A
lipid mediators like free FAs
steroid receptor family
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
-
mechanism of steroid hormone action
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
which subunit is responsible for the ion pore in voltage gated sodium channels
alpha
inhibitors of voltage gated sodium channels
local anesthetics
antiarrhythmic drugs
drugs used for treatment of epilepsy
voltage gated calcium channels targets of drugs for use of
hypertension, arrhythmias, ischemic herat disease
