Disrupting the Role of Biophysics in Drug Discovery: The NanoTemper Dianthus, A Medium Throughput Biophysical Screening Platform


T Alleyne-Weir1; A O'Keeffe2; C Morton1; J Wolf1; R Yan1; T Askwith1; N Bland1
1 Domainex Ltd, UK;  2 Damainex Ltd, UK


Biophysical assays have revolutionised the drug discovery
process. However, many biophysical assays are hampered by limited throughput,
which has led to them being most often deployed for hit characterisation and
orthogonal screening.  Domainex has invested in two disruptive
technologies that massively increase the throughput of quantitative,
biophysical assays: Grating Coupled Interferometry (Creoptix Wave) and the
NanoTemper Dianthus.

The Dianthus is a plate-based, in-solution binding assay, which
employs Temperature Related Intensity Changes (TRIC) in fluorescence intensity
to quantify ligand binding.  The Dianthus is suitable for single
concentration screening and the determination of true KD values. The
sensitivity of the Dianthus pico detector allows for assaying at low nanomolar
to high picomolar concentrations of protein, meaning that Dianthus assays can
scale in a way many other biophysical approaches cannot.

Here we describe employing the Dianthus in two screening
projects: a Medium Throughput Screen of 20,000 compounds and a fragment screen,
demonstrating the flexibility and power of this assay platform.

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