Journal article
In depth analysis of kinase cross screening data to identify CaMKK2 inhibitory scaffolds
SN O’Byrne, JW Scott, JR Pilotte, AS da Santiago, CG Langendorf, JS Oakhill, BJ Eduful, RM Couñago, CI Wells, WJ Zuercher, TM Willson, DH Drewry
Molecules | MDPI | Published : 2020
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..
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Funding Acknowledgements
This research was funded in part by the National Cancer Institute of the National Institutes of Health to D.H.D. (grant number R01CA218442) and was supported by the NIH Illuminating the Druggable Genome program (grant number 1U24DK116204-01), FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) (2013/50724-5 and 2014/50897-0) and CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) (465651/2014-3). The SGC is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766], Janssen, Merck KGaA Darmstadt Germany, MSD, Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, Takeda, andWellcome [106169/ZZ14/Z]. J.W.S. and J.S.O. are funded by National Health and Medical Research Council (NHMRC) grants (GNT1138102) and (GNT1145265), respectively. A.A.S. is a FAPESP post-doctoral fellow (2019/14275-8). C.G.L. is an NHMRC early career fellow (GNT1143080).