biostudies-literatureDavis-Gilbert ZWInnovative Medicines InitiativeCancer Research UKEshelman Institute for Innovation, University of North CarolinaNIDDK NIH HHSFondation LeducqFunda??o Amaz?nia Paraense de Amparo ? PesquisaU.S. Department of DefenseCanada Foundation for InnovationNational Institutes of HealthNorth Carolina Biotechnology CenterGenome CanadaOntario Genomics Institute432-441https://www.ebi.ac.uk/biostudies/studies/S-EPMC10108397biostudies-literatureUnknown14(4)Naphthyridine-based inhibitors were synthesized to yield a potent and cell-active inhibitor of casein kinase 2 (CK2). Compound <b>2</b> selectively inhibits CK2α and CK2α' when profiled broadly, thereby making it an exquisitely selective chemical probe for CK2. A negative control that is structurally related but lacks a key hinge-binding nitrogen (<b>7</b>) was designed on the basis of structural studies. Compound <b>7</b> does not bind CK2α or CK2α' in cells and demonstrates excellent kinome-wide selectivity. Differential anticancer activity was observed when compound <b>2</b> was profiled alongside a structurally distinct CK2 chemical probe: SGC-CK2-1. This naphthyridine-based chemical probe (<b>2</b>) represents one of the best available small molecule tools with which to interrogate biACS medicinal chemistry lettersDiscovery of a Potent and Selective Naphthyridine-Based Chemical Probe for Casein Kinase 2.PMC10108397U24DK116204AL190107U24 DK1162042018-IDG-1030Dunford JEHavener TMOppermann UDrewry DHWells CIAxtman ADHowell SBashore FMHossain MAKramer ASmith JLSenbabaoglu FDavis-Gilbert ZWfalseDiscovery of a Potent and Selective Naphthyridine-Based Chemical Probe for Casein Kinase 2.Naphthyridine-based inhibitors were synthesized to yield a potent and cell-active inhibitor of casein kinase 2 (CK2). Compound <b>2</b> selectively inhibits CK2α and CK2α' when profiled broadly, thereby making it an exquisitely selective chemical probe for CK2. A negative control that is structurally related but lacks a key hinge-binding nitrogen (<b>7</b>) was designed on the basis of structural studies. Compound <b>7</b> does not bind CK2α or CK2α' in cells and demonstrates excellent kinome-wide selectivity. Differential anticancer activity was observed when compound <b>2</b> was profiled alongside a structurally distinct CK2 chemical probe: SGC-CK2-1. This naphthyridine-based chemical probe (<b>2</b>) represents one of the best available small molecule tools with which to interrogate bi2023-01-01T00:00:00Z2023 Apr2026-05-29T03:36:32.678Z2025-04-06T19:10:48.018ZS-EPMC101083973707738510.1021/acsmedchemlett.2c00530