Development of a potent and selective chemical probe for the pleiotropic kinase CK2

Highlights

• We developed a potent, selective, and cell-active chemical probe for CK2

• We identified a negative control compound to be used with the CK2 probe

• Our selective chemical probe (SGC-CK2-1) is not broadly antiproliferative

• SGC-CK2-1 is the best available chemical tool to define the roles of CK2 in cells

Summary

Building on the pyrazolopyrimidine CK2 (casein kinase 2) inhibitor scaffold, we designed a small targeted library. Through comprehensive evaluation of inhibitor selectivity, we identified inhibitor 24 (SGC-CK2-1) as a highly potent and cell-active CK2 chemical probe with exclusive selectivity for both human CK2 isoforms. Remarkably, despite years of research pointing to CK2 as a key driver in cancer, our chemical probe did not elicit a broad antiproliferative phenotype in >90% of >140 cell lines when tested in dose-response. While many publications have reported CK2 functions, CK2 biology is complex and an available high-quality chemical tool such as SGC-CK2-1 will be indispensable in deciphering the relationships between CK2 function and phenotypes.