Related Experiment Video
Updated: Jan 16, 2026
Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
Published on: June 30, 2019
Development of a chemical probe to enable characterization of the casein kinase 1γ subfamily
Jacob L Capener1, Thomas W Kramer1, Frances M Bashore1
1Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Abstract:
The casein kinase 1γ (CK1γ) subfamily, while severely understudied, is implicated in diverse disease-relevant pathways, including WNT signaling and human cytomegalovirus (HCMV) replication. While genetic tools exist to study CK1γ, the selective inhibition of CK1γ through pharmacological means remains underexplored. Chemical probes, or potent and selective inhibitors, remain one of the most powerful pharmacological tools for uncovering protein biology. Herein, we developed several novel assays for assessing target engagement with the CK1γ subfamily in cells. Enabled by these assays, we conducted a comprehensive structure-activity relationship (SAR) campaign to develop the first chemical probe, SGC-CK1γ-1, for the CK1γ subfamily. SGC-CK1γ-1, which was developed alongside a structurally related negative control compound, potently and selectively inhibited the CK1γ kinases in living cells, plus inhibited both WNT signaling and human cytomegalovirus replication.
