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Microscale Thermophoresis (MST) as a novel, alternative biophysical method for fragment screening and hit profiling

Fragment-based drug discovery (FBDD) relies on sensitive high-throughput screening technologies to quickly and reliably generate hits against a target. MST is a recently established biophysical method for measuring the binding of small molecules to a macromolecule. It is sensitive, solution-based, low-consumption and relatively high-throughput making it ideal for the screening of low molecular weight fragments against a target of interest.
Here, we demonstrate an in-house fragment screening project using MST against the immuno-oncology target indoleamine 2,3-dioxygenase 1 (IDO1). We provide follow-up data gathered from a complementary, orthogonal biochemical assay and near-neighbour SAR-by-library work which validates the fragment hits and the MST screening approach as a whole.

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