Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTV298Y)

• DTT Name: Calmodulin-dependent kinase II (CAMKK2)
• Synonyms: KIAA0787; Calcium/calmodulin-dependent protein kinase kinase beta; Calcium/calmodulin-dependent protein kinase kinase 2; CaMKK beta; CaMKK 2; CaM-kinase kinase beta; CaM-kinase kinase 2; CaM-KK beta; CaM-KK 2; CAMKKB
• Gene Name: CAMKK2
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Kinase
• UniProt ID: KKCC2_HUMAN
• TTD ID: T82262
• EC Number: EC 2.7.11.17
• Sequence:
  MSSCVSSQPSSNRAAPQDELGGRGSSSSESQKPCEALRGLSSLSIHLGMESFIVVTECEP
  GCAVDLGLARDRPLEADGQEVPLDTSGSQARPHLSGRKLSLQERSQGGLAAGGSLDMNGR
  CICPSLPYSPVSSPQSSPRLPRRPTVESHHVSITGMQDCVQLNQYTLKDEIGKGSYGVVK
  LAYNENDNTYYAMKVLSKKKLIRQAGFPRRPPPRGTRPAPGGCIQPRGPIEQVYQEIAIL
  KKLDHPNVVKLVEVLDDPNEDHLYMVFELVNQGPVMEVPTLKPLSEDQARFYFQDLIKGI
  EYLHYQKIIHRDIKPSNLLVGEDGHIKIADFGVSNEFKGSDALLSNTVGTPAFMAPESLS
  ETRKIFSGKALDVWAMGVTLYCFVFGQCPFMDERIMCLHSKIKSQALEFPDQPDIAEDLK
  DLITRMLDKNPESRIVVPEIKLHPWVTRHGAEPLPSEDENCTLVEVTEEEVENSVKHIPS
  LATVILVKTMIRKRSFGNPFEGSRREERSLSAPGNLLTKKPTRECESLSELKEARQRRQP
  PGHRPAPRGGGGSALVRGSPCVESCWAPAPGSPARMHPLRPEEAMEPE
• Function: Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching.
• KEGG Pathway:
  Autophagy - animal (hsa04140)
  AMPK signaling pathway (hsa04152)
  Longevity regulating pathway (hsa04211)
  Adipocytokine signaling pathway (hsa04920)
  Oxytocin signaling pathway (hsa04921)
  Alcoholic liver disease (hsa04936)
  Alcoholism (hsa05034)
• Reactome Pathway:
  CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde (R-HSA-442729)
  Activation of RAC1 downstream of NMDARs (R-HSA-9619229)
  Activation of AMPK downstream of NMDARs (R-HSA-9619483)
  CaMK IV-mediated phosphorylation of CREB (R-HSA-111932)

Molecular Interaction Atlas (MIA) of This DTT

3 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CQ7	DMXP073	N. A.	N. A.	Patented	[2]
US9623028, Compound 101	DM6F7M2	N. A.	N. A.	Patented	[2]
US9623028, Compound 79	DMMSHX4	N. A.	N. A.	Patented	[2]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID22136433C20	DMI8217	Discovery agent	N.A.	Investigative	[3]
STO609	DMZSOG2	Discovery agent	N.A.	Investigative	[1]

References

• [1] STO-609, a specific inhibitor of the Ca(2+)/calmodulin-dependent protein kinase kinase. J Biol Chem. 2002 May 3;277(18):15813-8.
• [2] Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof. US9623028.
• [3] 7,8-dichloro-1-oxo-beta-carbolines as a versatile scaffold for the development of potent and selective kinase inhibitors with unusual binding modes. J Med Chem. 2012 Jan 12;55(1):403-13.