Download MendeleyDevelopment of a potent and selective chemical probe for the pleiotropic kinase CK2.
Wells, C.I., Drewry, D.H., Pickett, J.E., Tjaden, A., Kramer, A., Muller, S., Gyenis, L., Menyhart, D., Litchfield, D.W., Knapp, S., Axtman, A.D.(2021) Cell Chem Biol 28: 546-558.e10
- PubMed: 33484635
- DOI: https://doi.org/10.1016/j.chembiol.2020.12.013
- Primary Citation of Related Structures:
6Z83, 6Z84 - PubMed Abstract:
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.
Organizational Affiliation:
Structural Genomics Consortium (SGC), UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, NC 27599, USA; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, UNC-CH, Chapel Hill, NC 27599, USA.
