Please wait while the transcript is being prepared...
0:00
My name is Dr. Wayne Carter.
This lecture is entitled
In Vitro Drug Screening.
0:08
Systematic Screening Rationale.
For compounds with potential
biological efficacy,
there's a need to
assess their activity,
and this is further
tested and validated
using specific biochemical
and cellular assays.
0:25
Bioassays.
Bioassays are
undertaken to establish
a concentration-response
curve for the drug
to target binding.
They determine the
effective dose (ED)
or inhibitor concentration
(IC) responses
that relate to drug potency.
Ideally, they should be
rapid, cost-effective,
and facilitate high-throughput
drug screening methods.
An example is
spectrophotometric measurements
of enzymatic activity,
in which a concentration
curve for drug binding
is considered with associated
enzymatic inhibition,
and these are performed
in microtitre plates.
For example, the one shown
is a 384-well plate.
You can get ones
that are 96-well,
or even 1000 or more wells.
1:14
Drug-Target Binding.
An example,
central nervous system
(CNS) drug assessment
as inhibition of cholinesterase,
so cholinesterase inhibitors,
and this is the first-line
treatment for Alzheimer's disease.
In the panel, we have
a concentration curve
of inhibition of
butyrylcholinesterase
by ethopropazine hydrochloride.
On the y-axis is
optical density.
This is a spectrophotometric
colour assay
in which there is an
increase in coloured product
depending on the
enzymatic activity.
The ethopropazine
hydrochloride is present
at between nought
and 30 nanomolar.
With increasing
drug concentration,
there's a flattening of the line
consistent with more
enzymatic inhibition.
