[ELRIG Drug Discovery EU 2021] High-Throughput Screening (HTS) Cascade to Generate Selective and High-Value Hits for PIM Kinase

[ELRIG Drug Discovery EU 2021] High-Throughput Screening (HTS) Cascade to Generate Selective and High-Value Hits for PIM Kinase
File Name/Number:
ELRIG Drug Discovery EU

Year:
2021

 

The proto-oncogene Proviral Integration site for Moloney murine leukemia virus 3 Kinase (PIM3K) is a protooncogene serine/threonine-protein kinase involved in numerous cancers. Identification of new PIM kinase inhibitor scaffolds is therefore highly valuable for the development of new anticancer therapies.

Kinase discovery efforts are usually particularly challenging, because of conserved active sites and high structural homology between kinases leading to safety liabilities. Here we present a comprehensive and robust screening cascade to rapidly identify selective PIM3 kinase inhibitors from our proprietary libraries. Moreover, subsequent to primary screening, novel PIM3K inhibitors can be profiled in analogous selectivity assays and confirmed in both orthogonal and cellular target engagement (TE) assays.