Abstract

High throughput screening (HTS) is the process by which large
diverse compound libraries are tested in an automated fashion to determine
their activity against specific biological targets or processes. The primary
goal of an HTS is to identify multiple progressable hit chemical series suitable
for optimisation through the subsequent hit to lead stage of a drug discovery
project. HTS is a dynamic synergy of scientific disciplines - medicinal
chemistry, biology, informatics and advanced automation technology.

At Sygnature Discovery, a tailor-made
internal HTS system has been set up using industry-leading vendors to allow us
to expand our screening capabilities to clients.  Our state of the art system is equipped with a
HighRes® Biosolutions
robotic workstation, a fully integrated informatics platform to ensure data fidelity and
compound tracking, liquid handling platforms including Labcyte Echo 550
acoustic dispensers and a custom compound storage unit, allowing us to execute HTS projects with speed and accuracy to ensure
the rapid and precise identification of hits.

Past experience has shown us that the quality and
nature of an HTS compound library is key to finding progressable hit series and
with this in mind we have designed a custom LeadFinder compound library of 150,000
structurally diverse compounds. This library is available to clients for
screening and offers novel structures with attractive lead-like properties.
Furthermore, compound stocks routinely undergo thorough quality control checks by
LC/MS to ascertain and monitor compound stability and integrity.

Herein, we describe the evolution of compound
screening at Sygnature Discovery, from small scale semi-automated small
molecule compound libraries through to the establishment of a fully automated,
state of the art HTS facility.