lecture 2 Flashcards
B and h2, nucleo anti metabolites makers were awarded Nobel prize because?
examples of receptor pharmacology and biochemistry & NOT structure
what were the first 2 receptors antagonists founded? targeted what?
pronethalol and propranolol–> Beta
what is receptor theory?
receptors must have structural and steric specificity
saturable and finite
high affinity for endogenous ligand at good conditoins
induce chemical event
what are a and b andrerecerpors? and what was founded?
G protein coupled
used isoprenaline to develop a B receptors antagonist to lover blood pressure
what are GPCR structural features?
7 transmembrane domain –interact with ligands
extracelular region–N terminus, involved in binding and recognize
intracellular region–C terminis, itnereact w/ G proteins and intracellular signaling
G proteins: transmit signal, ABG units
Lingan binding: extraceullar membrane, binds to ligands
what is GPCR function?
ligand binding and activation
G protein activation
signal transduction
effector activation
termination
what are antimetabolites? classes?
what was first antimetabolite?
inhibit use of endogenous metabolite
nucleobase analogs
nucleoside analogues–treat cancer and infections
antifolates– treat cancer
sulfanilamide
what does DHFR do?
what was developed by elion and hitchins to target DHFR?
coverts dihydrofolate—> tetrahydrofolate
trimethoprim
what as hypothesis of nuclease analogues?
antimetabolics based on nucleotides cold be used as therapeutics to target bad nucleic acid metabolism in disease
what was antimetabolic discovery assay?
bacteria could grow with thyme and purine–> syn purine if given folic acid
identify purine analog that inhibit growth via inhibiting nuclei acid metabolic
—determine spec by competing w purine to see if growth inhibitory could be reversed
what are thiopurine and what does it lead to?
prodrugs that activation HGPRT to ribonucleotide
inhibits aminophosphoribsyl transferase–> lower AMP and GMP
mis incoporated RNA or DNA–> apoptosis
prodrug & active drug undergo S methylation via TPMT
activation & activation*
what are two other targets of anti metabolites?
DNA poly inhibitors
reverse transcriptase
what is ligand based drug design?
new ligand based on known old ligand
need active & inactive molecules to find pharmacophore (model of binding site)
computational with tools
what is structure based drug design?
design of new ligand based on known ligands by knowledge of biding site
needs high resolution of structure relevant target ligand complex
uses software to help
examples of SBDD?
first drug from SBDD?
other drugs?
captopril–angiotensin converting enzymes inhibitor
dorzolamide
Imatinib– tyrosine kinase inhibitor
cimetidine– H2r antagonist
SBDD–> neuraminidase inhibitor
oseltamivir
zanamivir–
both for influenza
what are reverse agonist?
type of ligand that binds to a receptor and reduces its basal activity
