PMID- 31941153
OWN - NLM
STAT- MEDLINE
DCOM- 20201007
LR  - 20231113
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 25
IP  - 2
DP  - 2020 Jan 13
TI  - In Depth Analysis of Kinase Cross Screening Data to Identify CAMKK2 Inhibitory 
      Scaffolds.
LID - 10.3390/molecules25020325 [doi]
LID - 325
AB  - 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.
FAU - O'Byrne, Sean N
AU  - O'Byrne SN
AD  - Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of 
      North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
FAU - Scott, John W
AU  - Scott JW
AD  - St Vincent's Institute and Department of Medicine, The University of Melbourne, 
      41 Victoria Parade, Fitzroy 3065, Australia.
AD  - Mary MacKillop Institute for Health Research, Australian Catholic University, 215 
      Spring Street, Melbourne 3000, Australia.
AD  - The Florey Institute of Neuroscience and Mental Health, 30 Royal Parade, 
      Parkville 3052, Australia.
FAU - Pilotte, Joseph R
AU  - Pilotte JR
AD  - Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of 
      North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
FAU - Santiago, Andre da S
AU  - Santiago ADS
AD  - Centro de Quimica Medicinal (CQMED), Centro de Biologia Molecular e Engenharia 
      Genetica (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP 
      13083-875, Brazil.
AD  - Structural Genomics Consortium, Departamento de Genetica e Evolucao, Instituto de 
      Biologia, UNICAMP, Campinas, SP 13083-886, Brazil.
FAU - Langendorf, Christopher G
AU  - Langendorf CG
AD  - St Vincent's Institute and Department of Medicine, The University of Melbourne, 
      41 Victoria Parade, Fitzroy 3065, Australia.
FAU - Oakhill, Jonathan S
AU  - Oakhill JS
AD  - St Vincent's Institute and Department of Medicine, The University of Melbourne, 
      41 Victoria Parade, Fitzroy 3065, Australia.
AD  - Mary MacKillop Institute for Health Research, Australian Catholic University, 215 
      Spring Street, Melbourne 3000, Australia.
FAU - Eduful, Benjamin J
AU  - Eduful BJ
AD  - Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of 
      North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
FAU - Counago, Rafael M
AU  - Counago RM
AD  - Centro de Quimica Medicinal (CQMED), Centro de Biologia Molecular e Engenharia 
      Genetica (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP 
      13083-875, Brazil.
AD  - Structural Genomics Consortium, Departamento de Genetica e Evolucao, Instituto de 
      Biologia, UNICAMP, Campinas, SP 13083-886, Brazil.
FAU - Wells, Carrow I
AU  - Wells CI
AD  - Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of 
      North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
FAU - Zuercher, William J
AU  - Zuercher WJ
AD  - Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of 
      North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
FAU - Willson, Timothy M
AU  - Willson TM
AD  - Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of 
      North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
FAU - Drewry, David H
AU  - Drewry DH
AD  - Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of 
      North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
LA  - eng
GR  - P30 CA016086/CA/NCI NIH HHS/United States
GR  - R01 CA218442/CA/NCI NIH HHS/United States
GR  - 1U24DK116204-01/NH/NIH HHS/United States
GR  - R01CA218442/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20200113
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Benzimidazoles)
RN  - 0 (Naphthalimides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (STO 609)
RN  - EC 2.7.11.17 (CAMKK2 protein, human)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase)
SB  - IM
MH  - Animals
MH  - Benzimidazoles/*chemistry
MH  - *Calcium-Calmodulin-Dependent Protein Kinase Kinase/antagonists & 
      inhibitors/chemistry
MH  - Humans
MH  - Naphthalimides/*chemistry
MH  - Protein Kinase Inhibitors/*chemistry
PMC - PMC7024175
OTO - NOTNLM
OT  - CAMKK2
OT  - STO-609
OT  - chemical probes
OT  - kinase
OT  - kinase inhibitors
OT  - oncology
COIS- The authors declare no conflict of interest.
EDAT- 2020/01/17 06:00
MHDA- 2020/10/08 06:00
PMCR- 2020/01/13
CRDT- 2020/01/17 06:00
PHST- 2019/12/19 00:00 [received]
PHST- 2020/01/07 00:00 [revised]
PHST- 2020/01/08 00:00 [accepted]
PHST- 2020/01/17 06:00 [entrez]
PHST- 2020/01/17 06:00 [pubmed]
PHST- 2020/10/08 06:00 [medline]
PHST- 2020/01/13 00:00 [pmc-release]
AID - molecules25020325 [pii]
AID - molecules-25-00325 [pii]
AID - 10.3390/molecules25020325 [doi]
PST - epublish
SO  - Molecules. 2020 Jan 13;25(2):325. doi: 10.3390/molecules25020325.