what are the 3 main stages of drug discovery
target and lead discovery phase
pre-clinical discovery phase
clinical development and marketing
what are all the stages on the drug discovery process
gene discovery
target validation and assay dev
lead identification
lead optimisation
pre clinical
phase 1
phase 2
phase 3
what may affect the success of experiements
adme in body
variation in receptor in body
pka/ph
why are not all chemicals drugs
no pharmacophore
no target
what are the requirements for a good drug target
no uniform distribution of taret in body
available specific biomarker
good IP characteristics
target is disease modifying
favourable prediction of potential SE
favourable assayability for high throughput screening
what are the 3 phases of drug action
pharmaceutical phase (physicochemical )
pharmacokinetic (ADME)
pharmacodynamic (pharmacological activity)
what are the lipinski rule of 5
5 H bond donors
10 H bond acceptors
MW<500
cLogp < 5
what is a pharmacophore
ensures optimal interaction with specific biological target structure for biological response
what is an auxophore
not essential for binding ; might confer physicochemical properties / helps to hold pharmacophore in appropriate place / conversion form prodrug / bioconjugates
where is the pharmacophoric triangle located in the 3D triangle of the aryloxypropanolmine
between centre of benzene ring, +ve charged N of amine and OH group
dissociation of drug leads to
+ve S and + H
smaller kd means
better binding and stringer drug effect
what is selectivity in the expression of drug effects
IC50(host) / IC50 (pathogen)
what is IC50
the [drug] required to inhibit 50% of the measured activity
what can SAR studies be used for
optimise pharmacological activity (improve potency)
optimise ADME profiles (improve PK)
optimise therapuetic index (improve toxicophore)
the higher the C the ___ the IC50
higher
the higher the C the ___ the log 1/C
lower
