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Flashcards in Drug Targets Deck (25):

Transcription factors:

-promote or inhibit what?

-defining feature?

-what is the response element?

-promote or inhibit the recruitment of RNA polymerase to specific genes

-defining feature is the presence of the DNA-binding domain

-response element is the specific DNA sequence the TF binds to 


GPCR ligands

Biogenic amines:


acetylcholine, epinephrine, norepinephrine, dopamine, serotonin, histamine


GPCR ligands



adrenocorticotropin, angiotensin, bradykinin, opioids


GPCR Ligands

Amino acids

glutamate, GABA


GPCR Ligands



leukotrienes, prostacyclin, TxA2


GPCR ligands



adenosine, ADP, ATP


Structure of GPCR:

-transmembrane domain 

-N terminal domain (extracellular) often is what?

-C-terminal domain (cytosolic) contains multiple what?

-cytoplasmic loops contain?

-7 TM domain formed by a single polypeptide chain

-N-terminal domain is often glycosylated

-C-terminal domain contains multiple phosphorylation sites (serine/threonine residues)

-cytoplasmic loops contain G-protein binding sites


G-protein cycle:

-Six Steps

1. basal unstimulated state

2. Agonist activates receptor

3. which promotes release of GDP from the G Protein

4. Allows entry of GTP into nucleotide binding site

5. Signal terminated by hydrolysis of GTP

6. Return of system to (1)

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Classification of G-protein families based on what?

based on Ga subunit-induced effects


Gs GGq

-effect on adenylyl cyclase and Src tyrosine kinase

Gs activates all isoforms of adenylyl cyclase and Src tyrosine kinase

Gi inhibits adenylyl cyclases but activates tyrosine kinase Src

Gq activates phospholipase Cß


cAMP second messenger pathway

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Ca2+-phosphoinositide signaling pathway

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Receptors w/ Intrinsic Enzyme Activity:


IGF-1, Insulin, VEGF, EGF, NGF, PDGF


Structure of RTKs

-exception to general rule

most RTKs possess a single polypeptide chain, but insulin and IGF receptors have 2 chains, alpha and beta, linked by a disulfide bond

-ligand-binding shows very little similarity between members of the family, but the tyrosine kinase domain is similar


Mechanism of activation of the epidermal growth factor receptor:

-what happens upon binding?

-what happens when cytoplasmic domain becomes phosphorylated?

-upon binding of EGF (circle), the receptor converts from its inactive monomeric state (left) to an active dimeric state (right), in which two receptor polypeptides bind noncovalently.

-the cytoplasmic domains become phosphorylated (P) on specific tyrosine residues (Y), and their enxymatic activities are activated, catalyzing phosphorylation of substrate proteins (S)

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-what kind of RTK?

-transmits the effect of which hormones/cytokines? (x5)

-it is a receptor coupled to cytosolic protein kinases

-transmits GH (somatotropin), Erythropoeietin, Leptin, Interferons, Interleukins 2 through 10, 15



JAK-STAT mechanism

come back to this one


Nuclear Receptors:

ligands: four examples

ligands are lipophilic molecules that can cross cell membrane

-examples include: steroids, thyroids, Vit D,A, and Lipid mediators such as FFAs and their products


Nuclear receptors:

-lag period?

-persistence of effects?

produce their effects after a lag period, effects can persist after the agonist concentration has been reduced to zero


Mechanism of steroid hormone action:

-how many domains does nuclear receptor polypeptide have?

-hsp90 binds to what?

-binding of a hormone causes?

-three domains

-hsp90 binds to the receptor in the absence of hormone and prevents folding into the active conformation of the receptor

-binding of a hormone (steroid) causes dissociation of the hsp90 stabilizer and permits conversion to the active configuration

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Voltage gated sodium channels:

-which subunits?

-drug examples that inhibit these channels

-composed of alpha and beta subunits

-examples of drugs include local anesthetics, antiarrhythmic drugs, drugs used for epilepsy treatment


voltage gated Ca2+ channels

-where are L type channels located?

-targets of what kind of drugs

located on cardiac and smooth muscle cells, targets of widely used drugs, calcium channel blockers or calcium antagonists (verapamil)


Direct Ligand-Gated Ion Channels:


-excitatory vs inhibitory

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

Excitatory NTs open cation channels (ACH, Glutamate)

Inhibitory NTs open anion channels (GABA, Glycine)


Nicotinic Acetylcholine receptors:

-activation causes what?

-structure and location

-activation induces inward sodium influx and membrane depolarization

-petameric receptors with two major locations: skeletal muscle and neuronal cells


GABA-A receptors:

-cause inward flux of what?

- GABAmediates synaptic inhibition where?


-Target for?



-Anionic channels causing inward Cl- influx and hyperpolarization

-mediate synpatic inhibition in CNS via these channels

-Pentameric structure

-target for inhalation GA drugs, IV GA drugs, Ethanol, Hypnotic/anti-anxiety benzos