Affiliation:
1. Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2. UNC Lineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Abstract
Protein kinase casein kinase 2 (CK2/CSNK2) is a pleiotropic kinase involved in many cellular processes and, accordingly, has been identified as a potential target for therapeutic intervention for multiple indications. Significant research effort has been invested into identifying CK2 inhibitors as potential drug candidates and potent and selective CK2 chemical probes to interrogate CK2 function. Here, we review the small molecule inhibitors reported for CK2 and discuss various orthosteric, allosteric, and bivalent inhibitors of CK2. We focus on the pyrazolo[1,5-a]pyrimidines and naphthyridines, two chemotypes that have been extensively explored for chemical probe development. We highlight the uptake and demonstrated utility of the pyrazolo[1,5-a]pyrimidine chemical probe SGC-CK2-1 by the scientific community in cellular studies. Finally, we propose criteria for an ideal in vivo chemical probe for investigating CK2 function in a living organism. While no compound currently meets these metrics, we discuss ongoing and future directions in the development of in vivo chemical probes for CK2.
Funder
Bayer AG
Boehringer Ingelheim
the Canada Foundation for Innovation
the Eshelman Institute for Innovation, Genentech, Genome Canada through the Ontario Genomics Institute
EU/EFPIA/OICR/McGill/KTH/Diamond
Innovative Medicines Initiative 2 Joint Undertaking
Janssen
Merck KGaA
Pfizer
the São Paulo Research Foundation-FAPESP
Takeda
NIH
DoD ALSRP
North Carolina General Assembly
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