Setup of an iterative compound screening program for SAR optimization of a kinase inhibitor
To support the medicinal chemistry phase for a new hit series we needed to perform weekly to bi-weekly screening of 15 to 20 compounds to determine the activity of the compounds in both biochemical assays and cellular assays.
A screening cascade was set up to determine IC50 values for the compounds in three assays within one week or two weeks to facilitate fast turnaround times for medicinal chemistry optimization. Chemists may test basic parameters such as the solubility of new compound series.
Every three months, an extended cycle is performed based on the progress of the discovery project. The additional assays may include selectivity screening on a large kinase panel, a counter assay, determination of the binding affinity, testing of PK parameters in mice, hERG binding, and others.