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In depth analysis of kinase cross screening data to identify CAMKK2 inhibitory scaffolds
Sean N. O’Byrne, John W. Scott, Joseph R. Pilotte, André de S. Santiago, Christopher G. Langendorf, Jonathan S. Oakhill, Benjamin J. Eduful, Rafael M. Couñago, View ORCID ProfileCarrow I. Wells, View ORCID ProfileWilliam J. Zuercher, View ORCID ProfileTimothy M. Willson, View ORCID ProfileDavid H. Drewry
doi: https://doi.org/10.1101/2020.01.08.883009
Sean N. O’Byrne
1Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ; ; ; ; ; ;
John W. Scott
2St Vincent’s Institute and Department of Medicine, The University of Melbourne, 41 Victoria Parade, Fitzroy, 3065, Australia.; ; ;
3Mary MacKillop Institute for Health Research, Australian Catholic University, 215 Spring Street, Melbourne, 3000, Australia
4The Florey Institute of Neuroscience and Mental Health, 30 Royal Parade, Parkville, 3052, Australia
Joseph R. Pilotte
1Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ; ; ; ; ; ;
André de S. Santiago
5Centro de Química Medicinal (CQMED), Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-875, Brazil
6Structural Genomics Consortium, Departamento de Genética e Evolução, Instituto de Biologia, UNICAMP, Campinas, SP, 13083-886, Brazil. ;
Christopher G. Langendorf
2St Vincent’s Institute and Department of Medicine, The University of Melbourne, 41 Victoria Parade, Fitzroy, 3065, Australia.; ; ;
Jonathan S. Oakhill
2St Vincent’s Institute and Department of Medicine, The University of Melbourne, 41 Victoria Parade, Fitzroy, 3065, Australia.; ; ;
3Mary MacKillop Institute for Health Research, Australian Catholic University, 215 Spring Street, Melbourne, 3000, Australia
Benjamin J. Eduful
1Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ; ; ; ; ; ;
Rafael M. Couñago
5Centro de Química Medicinal (CQMED), Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-875, Brazil
6Structural Genomics Consortium, Departamento de Genética e Evolução, Instituto de Biologia, UNICAMP, Campinas, SP, 13083-886, Brazil. ;
Carrow I. Wells
1Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ; ; ; ; ; ;
William J. Zuercher
1Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ; ; ; ; ; ;
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- ORCID record for William J. Zuercher
- For correspondence: seanobyrne@live.ie joseph.pilotte@unc.edu beduful@email.unc.edu carrow.wells@unc.edu william.zuercher@unc.edu tim.willson@unc.edu david.drewry@unc.edu
Timothy M. Willson
1Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ; ; ; ; ; ;
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- ORCID record for Timothy M. Willson
- For correspondence: seanobyrne@live.ie joseph.pilotte@unc.edu beduful@email.unc.edu carrow.wells@unc.edu william.zuercher@unc.edu tim.willson@unc.edu david.drewry@unc.edu
David H. Drewry
1Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ; ; ; ; ; ;
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- ORCID record for David H. Drewry
- For correspondence: david.drewry@unc.edu seanobyrne@live.ie joseph.pilotte@unc.edu beduful@email.unc.edu carrow.wells@unc.edu william.zuercher@unc.edu tim.willson@unc.edu david.drewry@unc.edu
Abstract
The calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) plays a central role in many cell signaling pathways. CAMKK2 activates CAMK1, CAMK4, AMPK, and AKT leading to numerous physiological responses. Deregulation of CAMKK2 is linked to several diseases, suggesting utility of CAMKK2 inhibitors for oncological, metabolic and inflammatory indications. In this work we review the role of CAMKK2 in biology and disease. Through analysis of literature and public databases we have identified starting points for CAMKK2 inhibitor medicinal chemistry campaigns. These starting points provide an opportunity for the development of selective CAMKK2 inhibitors and will lead to tools that delineate the roles of this kinase in disease biology.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Posted January 08, 2020.
In depth analysis of kinase cross screening data to identify CAMKK2 inhibitory scaffolds
Sean N. O’Byrne, John W. Scott, Joseph R. Pilotte, André de S. Santiago, Christopher G. Langendorf, Jonathan S. Oakhill, Benjamin J. Eduful, Rafael M. Couñago, Carrow I. Wells, William J. Zuercher, Timothy M. Willson, David H. Drewry
bioRxiv 2020.01.08.883009; doi: https://doi.org/10.1101/2020.01.08.883009
In depth analysis of kinase cross screening data to identify CAMKK2 inhibitory scaffolds
Sean N. O’Byrne, John W. Scott, Joseph R. Pilotte, André de S. Santiago, Christopher G. Langendorf, Jonathan S. Oakhill, Benjamin J. Eduful, Rafael M. Couñago, Carrow I. Wells, William J. Zuercher, Timothy M. Willson, David H. Drewry
bioRxiv 2020.01.08.883009; doi: https://doi.org/10.1101/2020.01.08.883009
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