lec 8. receptors Flashcards
disease modifying genes
genes involved with disease - 10% of genome
druggable genome
protein that has ligand binding site and whose activity is regulated by ligand binding
drug targets (+4 examples)
proteins that we can create drugs (small molecule or biologics) for
includes: receptors, ion channels, enzymes, and transporters
receptors as drug targets
drugs need to be specific to the receptor as there are mutliple subtypes
drugs: agonists, inverse agonist, antagonist
ion channels as drug targets
drugs: blockers (block pore), modulators (alter behaviour such as open probability)
enzymes as drug targets
proteins which create a product or which have a post translational modification
drugs: inhibitors, false substrate (produce abnormal metabolite), prodrug (have to be metabolized by enzyme to become active)
transporters as drug targets
carry things across membrane
drugs: inhibitor, false substrate (act as substrate to get carried across)
microtubules as protein targets
drugs:
colchicine - interferes with stability of MT and prevents inflammatory response in gout
paclitaxel - stabalises MT so cancer cells cant divide
receptor families
1) GPCRs - 7 TMD, needs G protein to transduce signal
2) Kinase-linked - 1 TMD, kinase signalling cascade
3) Nuclear receptor - 0 TMD, has DNA binding domain
4) Ligand gated ion channels - multiple TMD, ligand binding site and pore
ligand-gated ion channel families
1) Cys-loop Type - 4 TMD, pentameric, nAChR GABAr 5-HT
2) Ionotropic Glutamate - 3 TMD, tetrameric, NMDA
3) P2X Receptor - 2 TMD, trimeric, P2XR
4) Calcium Release - tetrameric, IP3r, RyR
biological drugs
proteins (endogenous, engineered, or antibodies)
oligonucleotides (RNA or DNA)
injected into bloodstream, works on surface of cells, very large, produced within specially engineered cells
gene therapy
addition of genetic material to cells to prevent/alleviate/or cure disease
small molecule drugs
smaller, interact inside cells, synthesized using chemical reactions
