druggable targets Flashcards
what is a receptor?
a protein involved in the normal process of cell communication within an organism
what can be a drug target?
-proteins: receptors, enzymes, transport proteins and ion transporters
-nucleic acids: DNA, RNA, and the ribosome
or miscellaneous e.g. antacids neutralise H+
how do enzyme inhibitors work? give an example
interfere with the conversion of substrate into product.
example: acetylsalicylic acid acts cyclooxygenase, converting arachidonic acid into active lipid product that interacts with prostaglandins
how do statins work?
simvastatin targets HMG-CoA reductase, competitively inhibiting it and interfering with de novo cholesterol synthesis
how do enzyme false substrates work?
they are recognised by the enzyme due to similar structure, but generate an abnormal product
how does a-methylDOPA work as a false enzyme substrate?
its coverted into a-methylnoradrenaline by DOPA decarboxylase/dopamine-B-hydroxylase
what do transporters do?
bind the substrate and alter to make it active, whilst moving it across the membrane
why are transporters required?
some molecules are too polar to permeate the membrane
what is a symport?
where the transport of organic molecules is coupled to the transport of ions in the same direction
what does a transporter false substrate do?
competes with normal substrate, leading to an accumulation of abnormal compound
give an example of a transporter inhibitor
cocaine
binds to monoamine transporters, inhibiting transport of NTs, causing the presence of NT outside the cell to remain high for longer
give an example of a transporter false substrate
amphetamine
transported into the noradrenaline/dopamine nerve terminal, causes extracellular NT to increase and increases NT release from vesicles
in which ways can drugs affect ion channels?
- binding to the channel protein itself
- by indirect interaction involving a G protein and other intermediaries
- by altering the expression of ion channels on the cell surface
how do ion channel blockers work?
they bind in the channel pore and affect ion permeation
how do ion channel modulators work?
they bind to the ion channel and affect gating, they can have a positive or negative effect on permeation in response to a ligand
what are ligand gated ion channels and what type of transmission are they responsible for?
a subfamily of ion channels that are regulated by the binding of a specific agonist to alter membrane permeability. they are involved in rapid transmission of a signal
what is a pro-drug?
a drug which requires chemical or enzymatic modification before becoming active
give an example of a pro-drug
enalapril - ACE converting enzyme inhibitor that is converted to the ACE inhibitor enalaprilat by cellular esterases
give an example of a drug which inhibits a transporter
H+ pump inhibitor esomeprazole
what is the difference between an ion channel blocker and an ion channel modulator?
blockers bind in the channel pore to affect ion permeation
modulators bind to the ion channel protein to affect gating
what is an example of an ion channel blocker?
tetrodotoxin - voltage gated sodium channel blocker from a puffer fish
what is an example of an ion channel modulator?
gliclazide - a sulfonylurea used in the treatment of diabetes type II. modulator of ATP sensitive potassium channels
what is salbutamol?
a B2-adrenoceptor selective agonist
what is a nuclear receptor?
a receptor for lipophilic signalling molecules. it can be located in the nucleus or the cytoplasm and act as transcriptional regulators
