(1021-B) Spectral Shift & MST-TRIC: New Biophysical Technologies Supporting Kinase Drug Discovery Programs

PIM3 Kinase, which belongs to the Ca2+/calmodulin-dependent protein kinase (CaMK) group, exhibits serine/threonine kinase activity. Similar to other members of the PIM family (i.e. PIM1 and PIM2), PIM3 can prevent apoptosis, promote cell survival and protein translation. In addition, identifying potent and selective hits for PIM3 is of particular interest for the treatment of cancer.

Using Eurofins Discovery’s state-of-the art hit finding platform, we designed different comprehensive screening cascades which biophysics is acting as primary screening (fragment-based screening approach) and/or orthogonal assays as SPR, MST, TSA, ITC, etc.

Several biophysical strategies can be used for this step of a drug discovery program, and it is the target properties which drive the selection of the most suitable technology. The novel Spectral Shift, using the Dianthus (well-known for the MST), was the most appropriate method for PIM3 drug-discovery program. It was important to implement an easy and rapid assay that would monitor the ability of PIM3 to bind natural ligand, compounds and fragments in solution. Using the Echo’s acoustic droplet ejection, nanoliter dispensing in 394-well plates, which vastly reduces sample consumption, robust data are quickly generated, driving the MedChem analysis for Hit-to-Lead step.