Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFYL58)

• DTT Name: CaM-kinase II (CAMK2)
• Synonyms: Calcium/calmodulin-dependent protein kinase type II; CaMK-II; CaM kinase II; CAMK
• Gene Name: CAMK2A
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: KCC2A_HUMAN ; KCC2B_HUMAN ; KCC2D_HUMAN ; KCC2G_HUMAN
• TTD ID: T18299
• Sequence:
  MATITCTRFTEEYQLFEELGKGAFSVVRRCVKVLAGQEYAAKIINTKKLSARDHQKLERE
  ARICRLLKHPNIVRLHDSISEEGHHYLIFDLVTGGELFEDIVAREYYSEADASHCIQQIL
  EAVLHCHQMGVVHRDLKPENLLLASKLKGAAVKLADFGLAIEVEGEQQAWFGFAGTPGYL
  SPEVLRKDPYGKPVDLWACGVILYILLVGYPPFWDEDQHRLYQQIKAGAYDFPSPEWDTV
  TPEAKDLINKMLTINPSKRITAAEALKHPWISHRSTVASCMHRQETVDCLKKFNARRKLK
  GAILTTMLATRNFSGGKSGGNKKSDGVKESSESTNTTIEDEDTKVRKQEIIKVTEQLIEA
  ISNGDFESYTKMCDPGMTAFEPEALGNLVEGLDFHRFYFENLWSRNSKPVHTTILNPHIH
  LMGDESACIAYIRITQYLDAGGIPRTAQSEETRVWHRRDGKWQIVHFHRSGAPSVLPH
• Function: CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release. Member of the NMDAR signaling complex in excitatory synapses it may regulate NMDAR-dependent potentiation of the AMPAR and synaptic plasticity.
• KEGG Pathway:
  ErbB signaling pathway (hsa04012)
  Calcium signaling pathway (hsa04020)
  cAMP signaling pathway (hsa04024)
  HIF-1 signaling pathway (hsa04066)
  Oocyte meiosis (hsa04114)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  Wnt signaling pathway (hsa04310)
  Circadian entrainment (hsa04713)
  Long-term potentiation (hsa04720)
  Neurotrophin signaling pathway (hsa04722)
  Cholinergic synapse (hsa04725)
  Dopaminergic synapse (hsa04728)
  Olfactory transduction (hsa04740)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Insulin secretion (hsa04911)
  GnRH signaling pathway (hsa04912)
  Melanogenesis (hsa04916)
  Oxytocin signaling pathway (hsa04921)
  Glucagon signaling pathway (hsa04922)
  Gastric acid secretion (hsa04971)
  Amphetamine addiction (hsa05031)
  Tuberculosis (hsa05152)
  Proteoglycans in cancer (hsa05205)
  Glioma (hsa05214)
• Reactome Pathway:
  Trafficking of AMPA receptors (R-HSA-399719)
  Ca2+ pathway (R-HSA-4086398)
  Unblocking of NMDA receptor, glutamate binding and activation (R-HSA-438066)
  CREB phosphorylation through the activation of CaMKII (R-HSA-442729)
  CREB phosphorylation through the activation of Ras (R-HSA-442742)
  Ras activation uopn Ca2+ infux through NMDA receptor (R-HSA-442982)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Interferon gamma signaling (R-HSA-877300)
  HSF1-dependent transactivation (R-HSA-3371571)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rimacalib	DMSC7TN	Rheumatoid arthritis	FA20	Phase 2	[1]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABIO 09-01	DM0LUOM	Anxiety disorder	6B00-6B0Z	Investigative	[2]
KN-93	DMPTMKH	Discovery agent	N.A.	Investigative	[3]
PMID18334293C15b	DM1I6AY	Discovery agent	N.A.	Investigative	[4]
PMID18337095C27	DMEOHLV	Discovery agent	N.A.	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	1.34E-02	-0.33	-0.93

References

• [1] Role for CaMKII inhibition in rheumatoid arthritis: effects on HIF-1-induced VEGF production by rheumatoid synovial fibroblasts. Ann N Y Acad Sci. 2009 Sep;1173:706-11.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1558).
• [3] Discovery of a 3-amino-6-phenyl-pyridazine derivative as a new synthetic antineuroinflammatory compound. J Med Chem. 2002 Jan 31;45(3):563-6.
• [4] Pyrimidine-based inhibitors of CaMKIIdelta. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2404-8.
• [5] Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 3: Importance of the indole orientation. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2399-403.