Here, we introduce a new ultra-high throughput biophysical screening instrument, the Dianthus™ uHTS and provide an example screening data set exploring small-molecule inhibitors targeting MEK1, a key kinase in the MAPK/ERK pathway.
The Dianthus uHTS platform enables ultra-high-throughput biophysical screening (approx. 250 000 data points per day) by detecting ligand interactions using Spectral Shift technology. In this study, we screened 5120 different compounds against MEK1, identifying 62 high priority hits by single dose screening and further 81 hits of a lower priority. The dose-response analysis confirmed 28 compounds with Kd values below 10 μM, including five with affinities sub 100 nM. Orthogonal validation on high priority compounds using thermal shift and ADP Glo assays further refined the hit list to 6 validated binders which also inhibit ATPase activity.
These results demonstrate the efficiency of Dianthus uHTS for rapid hit identification with minimal sample consumption, supporting its application in early-stage drug discovery.
