In depth analysis of kinase cross screening data to identify CaMKK2 inhibitory scaffolds
Journal article
O’Byrne, Sean N., Scott, John W., Pilotte, Joseph R., Santiago, André da S., Langendorf, Christopher G., Oakhill, Jonathan S., Eduful, Benjamin J., Couñago, Rafael M., Wells, Carrow I., Zuercher, William J., Willson, Timothy M. and Drewry, David H.. (2020). In depth analysis of kinase cross screening data to identify CaMKK2 inhibitory scaffolds. Molecules. 25(2), pp. 1-19. https://doi.org/10.3390/molecules25020325
Authors | O’Byrne, Sean N., Scott, John W., Pilotte, Joseph R., Santiago, André da S., Langendorf, Christopher G., Oakhill, Jonathan S., Eduful, Benjamin J., Couñago, Rafael M., Wells, Carrow I., Zuercher, William J., Willson, Timothy M. and Drewry, David H. |
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Abstract | The calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) activates CAMK1, CAMK4, AMPK, and AKT, leading to numerous physiological responses. The deregulation of CAMKK2 is linked to several diseases, suggesting the utility of CAMKK2 inhibitors for oncological, metabolic and inflammatory indications. In this work, we demonstrate that STO-609, frequently described as a selective inhibitor for CAMKK2, potently inhibits a significant number of other kinases. Through an analysis of literature and public databases, we have identified other potent CAMKK2 inhibitors and verified their activities in differential scanning fluorimetry and enzyme inhibition assays. These inhibitors are potential starting points for the development of selective CAMKK2 inhibitors and will lead to tools that delineate the roles of this kinase in disease biology. |
Keywords | kinase; CAMKK2; STO-609; chemical probes; oncology; kinase inhibitors |
Year | 2020 |
Journal | Molecules |
Journal citation | 25 (2), pp. 1-19 |
Publisher | Multidisciplinary Digital Publishing Institute (MDPI AG) |
ISSN | 1420-3049 |
Digital Object Identifier (DOI) | https://doi.org/10.3390/molecules25020325 |
Scopus EID | 2-s2.0-85077941406 |
Open access | Published as ‘gold’ (paid) open access |
Research or scholarly | Research |
Page range | 1-19 |
Funder | National Health and Medical Research Council (NHMRC) |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 13 Jan 2020 |
Publication process dates | |
Accepted | 08 Jan 2020 |
Deposited | 27 Apr 2021 |
Grant ID | NHMRC/1138102 |
NHMRC/1145265 | |
NHMRC/1143080 |
https://acuresearchbank.acu.edu.au/item/8vy63/in-depth-analysis-of-kinase-cross-screening-data-to-identify-camkk2-inhibitory-scaffolds
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Publisher's version
OA_OByrne_2020_In_depth_analysis_of_kinase_cross.pdf | |
License: CC BY 4.0 | |
File access level: Open |
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