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

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.

SUBMITTER: Wells CI

PROVIDER: S-EPMC8864761 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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

Wells Carrow I CI Drewry David H DH Pickett Julie E JE Tjaden Amelie A Krämer Andreas A Müller Susanne S Gyenis Laszlo L Menyhart Daniel D Litchfield David W DW Knapp Stefan S Axtman Alison D AD

Cell chemical biology 20210122 4

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 ...[more]

PMID: 33484635

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