Comparison of CX-4945 and SGC-CK2-1 as inhibitors of CSNK2 using quantitative phosphoproteomics: Triple SILAC in combination with inhibitor-resistant CSNK2

Menyhart, Daniel; Gyenis, Laszlo; Jurčić, Kristina; Roffey, Scott E.; Puri, Aakshi; Jovanović, Predrag; Szkop, Krzysztof J.; Pittock, Paula; Lajoie, Gilles; Axtman, Alison D.; Larsson, Ola; Topisirović, Ivan; Litchfield, David W.

doi:10.1016/j.crchbi.2023.100041

Cited by 9 publications

(6 citation statements)

References 97 publications

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“…This is consistent with a recent phosphoproteomic study where different CK2 substrates have been identified by enrichment analysis of SGC-CK2-1- and CX-4945- dependent phosphoproteomes. 79 Further studies will be required to characterize the mechanism of action of AB668, since we cannot exclude that AB668 might have CK2-independent effects due to interactions with off-targets outside the kinome.…”

Section: Discussionmentioning

confidence: 99%

Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket

Bancet,

Frem,

Jeanneret

et al. 2024

iScience

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Section: Discussionmentioning

confidence: 99%

Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket

Bancet,

Frem,

Jeanneret

et al. 2024

iScience

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“…Recently, Menyhart et al evaluated the selectivity of CX-4945 and SGC-CK2-1 via triple SILAC quantitative phosphoproteomics using human osteosarcoma U2OS cells expressing exogenous wild-type CSNK2A1 or an inhibitor-resistant triple mutant (TM, V66A/H160D/I174A) [83]. Only a minority of the phosphosites that were downregulated in response to CX-4945 treatment (15% at 4 h and 5% at 24 h) were found to be CSNK2A1dependent.…”

Section: Indoloquinazolines Such As Cx-4945mentioning

confidence: 99%

CK2 Inhibitors Targeting Inside and Outside the Catalytic Box

Day-Riley,

West,

Brear

et al. 2024

Kinases and Phosphatases

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CK2 is a protein kinase that plays an important role in numerous cellular pathways involved in cell growth, differentiation, proliferation, and death. Consequently, upregulation of CK2 is implicated in many disease types, in particular cancer. As such, CK2 has gained significant attention as a potential therapeutic target in cancer, and over 40 chemical probes targeting CK2 have been developed in the past decade. In this review, we highlighted several chemical probes that target sites outside the conventional ATP-binding site. These chemical probes belong to different classes of molecules, from small molecules to peptides, and possess different mechanisms of action. Many of the chemical probes discussed in this review could serve as promising new candidates for drugs selectively targeting CK2.

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“…The authors concluded based on their data that SGC-CK2-1 demonstrates significantly enhanced selectivity toward CSNK2A1 compared to CX-4945. Through the use of inhibitor-resistant CK2 cells in tandem with SGC-CK2-1, more than 300 CSNK2A1-dependent phosphosites were identified [2,10].…”

Section: Use Of Sgc-ck2-1 By the Community In Cell-based Studiesmentioning

confidence: 99%

“…Protein kinase casein kinase 2 (CK2/CSNK2) is a constitutively active, ubiquitously expressed Ser/Thr kinase with hundreds of reported substrates [1,2]. Accordingly, CK2 plays regulatory roles in most cellular processes, and it has been identified as a potential therapeutic target for diverse diseases, including cancer, viral infections, neurodegenerative disorders, and many others [3][4][5][6][7][8][9][10].…”

Section: Introduction 1ck2 General Structure and Small Molecule Bindi...mentioning

confidence: 99%

CK2 Chemical Probes: Past, Present, and Future

Ong,

Drewry,

Axtman

2023

Kinases and Phosphatases

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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.

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Comparison of CX-4945 and SGC-CK2-1 as inhibitors of CSNK2 using quantitative phosphoproteomics: Triple SILAC in combination with inhibitor-resistant CSNK2

Cited by 9 publications

References 97 publications

Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket

Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket

CK2 Inhibitors Targeting Inside and Outside the Catalytic Box

CK2 Chemical Probes: Past, Present, and Future

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