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Hight throughput screening in modern drug discovery
High throughput screening: an evolving paradigm in drug discovery
New technologies in high throughput screening are continually reshaping how researchers search,
screen, and validate new therapeutic candidates.
using it to screen genes responsible for
Scientists analyze HTS data obtained
IGH THROUGHPUT SCREENING
(HTS) is a technique for simul
specific cellular processes or disease states
from primary and secondary screens to
taneously
analyzing thousands
and to identify biomolecules involved
identify the most promising candidate for
of samples for biological activity
in molecular pathways.
further development.
HIGH THROUGHPUT SCREENING
(HTS) is a technique for simultaneously
analyzing thousands
of samples for biological activity
at the cellular, pathway, model organism,
To accelerate each step in HTS, scien
How HTS works
or molecular level (1). It is an essential
tists
have utilized automation, robotics,
method that has significantly accelerated
Researchers divide the HTS process in
miniaturized assay formats, and powerful
drug discovery in a cost-effective manner.
drug discovery into several steps: target
data analysis tools (3). For instance, auto
Researchers employ HTS to rapidly identify
identification, assay design, primary and
mation
and robotics aid in efficient sample
active compounds, proteins, genes, or anti
secondary screens, and data analysis (5).
preparation and dispensing, which signifi
bodies,
collectively known as hits, which
Target identification is a crucial step that
cantly
speeds up the process compared to
modulate a specific biomolecular pathway.
focuses on a specific biological target,
manual handling. The miniaturized assay
A screen is considered high throughput if
such as a protein, involved in a particular
format, such as the use of 1536-well plates,
it conducts over 10,000 assays per day (2),
disease mechanism. This target serves as
reduces reagent consumption and offer
while ultra high throughput screening can
the key focus for screening a large library
higher throughput. Powerful software and
conduct up to 100,000 assays per day (3).
of compounds. Subsequently, scientists
algorithms analyze large datasets generat
Researchers have traced the origins
design assays to measure the activity of
ed
from HTS, rapidly identifying the most
of HTS methods back to the mid-1980s,
compounds on the target. In primary
promising compounds.
primarily within the pharmaceutical
screening, they extensively screen librar
Trends and technological advances
industry, where Pfizer screened natural
ies,
such as combinatorial chemistry,
driving HTS
products using 96-well plates (4). At that
protein, genomics, and peptide libraries,
time, the use of 96-well plates, relative to
to identify compounds that interact with
Scientists have expanded the HTS meth
traditional methods, enhanced the pace of
the biological target. This step ensures that
odology
by introducing technological
drug discovery, as many compounds could
compounds or biological entities with poor
advances that facilitate more efficient
be assessed simultaneously for a particular
or no effect can be quickly eliminated from
and multiplexed screening. Using tradi
action. Over the last few decades, advances
further investigation, allowing scientists
tional
HTS methods, scientists had to
in automation, robotics, and miniaturiza
to concentrate solely on biologically rele
analyze each compound in a large library
tion
have led to a wider adoption of HTS
vant
compounds. Compounds identified as
at a single concentration, which was a
methods from pharmaceutical companies
hits in primary screens are further char
tedious and time-consuming process. In
to other research fields such as synthetic
acterized
in a more refined secondary
contrast, the development of a quantita
biology, tissue engineering, and regenera
screen, such as cell-based assays, absorp
tive
high throughput screening (qHTS)
tive
medicine. Recently, researchers have
tion,
distribution, metabolism, excretion,
strategy enabled them to test numerous
utilized HTS beyond compound libraries,
and toxicity assays, and biophysical assays.
compounds at multiple concentrations in a
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