Cellular Drug Targets Flashcards
(20 cards)
Give definition of a drug
A chemical substance that produces a specific biological effect in a living organism
What are the 4 main Drug targets?
Membrane carriers
Enzymes
Ion channels
Receptors
What are the 4 types of drug receptors?
G-protein coupled receptors
Ezyme-linked
Ion channels
Nuclear receptors
What is drug receptor theory?
Drugs bind to drug receptor to generate their biological effect
Receptor can be any 3-dimensional molecular structure
Whole process known as Cellular signal transduction
Give a very short simple process of how to go from drug to biological effect?
Receptor—>Drug-receptor complex—> Conformational Change–> Biological change
GCPR: Classification
How many domains,
What and where do they activate?
What are they associated with?
How fast do they act?
Give example?
7 transmembrane domains
Activate enzymes in cell membrane
GCPR associate with heterotrimeric G-proteins complexes in cell membrane
Quite fast-takes seconds.
Drug–>Receptor–>G-protein–>Enzymes
Adrenoceptor
What does heterotrimeric and metabotropic mean?
3 subunits: Alpha, Gamma, and Beta.
M: are involved in metabolic processes but always and not only.
Enzyme linked : Classification
What are the direct and indirect?
Direct or indirect activation of enzymes (without G)
Receptor Tyr kinases (RTKs)
and receptor Ser/Thr kinases RSTKs=direct
Cytokine receptor=indirect
How fast and what is the process of Enzyme linked?
Very slow takes hours
Drug binds to receptor, Receptor forms dimer, Activation of receptor enymes domain—>Receptor phosphorylates itself–>Phosphorylation cascade—>Change in genes->proteins.
Whats the differene between cytokine receptors and RTKs process?
Cytokine receptors:
Dont always dimerise
No enzyme activity itself
Drug binding leads to recruitment of enzymes e.g. non RTKs
Kinases involved in phosphorylation
There is also a indirect action, so it lacks an enzyme domain, e.g. cytokine receptor, they recruit other enzymes to do the job
Ion channels: Classification
Where are they found, Give an example, what is the mechanism.
Found in any membrane
Multiple subunits with central ‘pore’/’channel’
Operates via direct ‘gating’ mechanisms’
e.g. Nicotinic acetylcholine receptor (nAChR)
How fast and what is the process in simple terms of ion channels?
Very fast- takes milliseconds
Drug–>Recptor—>movement of ions
What does heteromulteric mean
THEY CAN HAVE DIFFERENT NUMBER OF SUBUNITS
Nuclear: classification
Where are they found
what is LBD and DBD
Give example
In cytosol or nucleus
LBD: ligand binding domain
DBD: DNA binding domain
Bind to DNA to modify gene transcription
e.g. oestrogen receptor
What is type 1 nulcear receptors?
Type 1: receptor in the cytosol, needs to be lipophilic to pass through the membrane it may or not dimerise.
LBD: modifies gene transcription
What is type 2 nuclear receptor?
Type 2 receptor in the nucleus, drug binding modulates activity of the receptor
Oestrogen receptor: is lipophilic
Receptor process that binds to DNA process will take hours
Oestrogen Is type 1
Thyroid is type 2—> levothyroxine treats hyperthyroidism idk blah blah lol
Ion channel:
Give:
Location
Structure
Mechanism
Effector
Time from Drug binding to effect
Receptor example
Endrogenous drug
Exogenous drug
Location: Any membrane
Structure: Oligomeric , central channel
Mechanism: Gating
Effector: Voltage-gated channels
Time from Drug binding to effect: milliseconds
Receptor example: nAChR
Endrogenous drug: Acetylcholine/GABA
Exogenous drug: Nicotine, Propofol
GPCRs:
Give:
Location
Structure
Mechanism
Effector
Time from Drug binding to effect
Receptor example
Endrogenous drug
Exogenous drug
Location: Plasma Membrane
Structure: 7-TM
Mechanism: G-protein
Effector: Cell signalling
Time from Drug binding to effect: Seconds/minutes
Receptor example: mAChR/ GABAb-R
Endrogenous drug: Acetylcholine/GABA
Exogenous drug: Muscarine/Baclofen
Enzyme-linked:
Give:
Location
Structure
Mechanism
Effector
Time from Drug binding to effect
Receptor example
Endrogenous drug
Exogenous drug
Location: Plasma membrane (usually)
Structure: Dimer
Mechanism: Enzyme
Effector: Gene transcription
Time from Drug binding to effect: Hours
Receptor example: InsR, IL-6R
Endrogenous drug: Insulin, IL-6
Exogenous drug: Mecaserim, Tocilizumab
Nuclear:
Give:
Location
Structure
Mechanism
Effector
Time from Drug binding to effect
Receptor example
Endrogenous drug
Exogenous drug
Location: Cytosol/Nucleus
Structure: Monomer/Dimer LBD&DBD
Mechanism: DNA binding
Effector: Gene trasncription
Time from Drug binding to effect: Hours
Receptor example: ER, TR
Endrogenous drug: Oestrogen, Thyroid Hormones
Exogenous drug: Tamoxifen, Levothyroxine
