Target Information

Target General Information

Top

Target ID

T18299 (Former ID: TTDI02008)

Target Name

CaM-kinase II (CAMK2)

Synonyms

Calcium/calmodulin-dependent protein kinase type II; CaMK-II; CaM kinase II; CAMK

Click to Show/Hide

Gene Name

CAMK2A; CAMK2B; CAMK2D; CAMK2G

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Rheumatoid arthritis [ICD-11: FA20]

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.

Click to Show/Hide

BioChemical Class

Kinase

UniProt ID

KCC2A_HUMAN ; KCC2B_HUMAN ; KCC2D_HUMAN ; KCC2G_HUMAN

Sequence

MATITCTRFTEEYQLFEELGKGAFSVVRRCVKVLAGQEYAAKIINTKKLSARDHQKLERE
ARICRLLKHPNIVRLHDSISEEGHHYLIFDLVTGGELFEDIVAREYYSEADASHCIQQIL
EAVLHCHQMGVVHRDLKPENLLLASKLKGAAVKLADFGLAIEVEGEQQAWFGFAGTPGYL
SPEVLRKDPYGKPVDLWACGVILYILLVGYPPFWDEDQHRLYQQIKAGAYDFPSPEWDTV
TPEAKDLINKMLTINPSKRITAAEALKHPWISHRSTVASCMHRQETVDCLKKFNARRKLK
GAILTTMLATRNFSGGKSGGNKKSDGVKESSESTNTTIEDEDTKVRKQEIIKVTEQLIEA
ISNGDFESYTKMCDPGMTAFEPEALGNLVEGLDFHRFYFENLWSRNSKPVHTTILNPHIH
LMGDESACIAYIRITQYLDAGGIPRTAQSEETRVWHRRDGKWQIVHFHRSGAPSVLPH

Click to Show/Hide

HIT2.0 ID

T32REB

Drugs and Modes of Action

Top

Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

Rimacalib

Drug Info

Phase 2

Rheumatoid arthritis

[2]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 1 Modulator drugs

Rimacalib

Drug Info

[1], [2]

Inhibitor

[+] 4 Inhibitor drugs

ABIO 09-01

Drug Info

[3]

KN-93

Drug Info

[4]

PMID18334293C15b

Drug Info

[5]

PMID18337095C27

Drug Info

[6]

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 24 KEGG Pathways	+
1	ErbB signaling pathway
2	Calcium signaling pathway
3	cAMP signaling pathway
4	HIF-1 signaling pathway
5	Oocyte meiosis
6	Adrenergic signaling in cardiomyocytes
7	Wnt signaling pathway
8	Circadian entrainment
9	Long-term potentiation
10	Neurotrophin signaling pathway
11	Cholinergic synapse
12	Dopaminergic synapse
13	Olfactory transduction
14	Inflammatory mediator regulation of TRP channels
15	Insulin secretion
16	GnRH signaling pathway
17	Melanogenesis
18	Oxytocin signaling pathway
19	Glucagon signaling pathway
20	Gastric acid secretion
21	Amphetamine addiction
22	Tuberculosis
23	Proteoglycans in cancer
24	Glioma
Reactome	[+] 9 Reactome Pathways	+
1	HSF1-dependent transactivation
2	Trafficking of AMPA receptors
3	Ca2+ pathway
4	Unblocking of NMDA receptor, glutamate binding and activation
5	CREB phosphorylation through the activation of CaMKII
6	CREB phosphorylation through the activation of Ras
7	Ras activation uopn Ca2+ infux through NMDA receptor
8	RAF/MAP kinase cascade
9	Interferon gamma signaling
WikiPathways	[+] 9 WikiPathways	+
1	ErbB Signaling Pathway
2	Calcium Regulation in the Cardiac Cell
3	EGF/EGFR Signaling Pathway
4	Myometrial Relaxation and Contraction Pathways
5	Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
6	BDNF signaling pathway
7	Integrated Pancreatic Cancer Pathway
8	Corticotropin-releasing hormone
9	B Cell Receptor Signaling Pathway

References

Top

REF 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.

REF 2

CaMKII inhibitors: from research tools to therapeutic agents. Front Pharmacol. 2014; 5: 21.

REF 3

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).

REF 4

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.

REF 5

Pyrimidine-based inhibitors of CaMKIIdelta. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2404-8.

REF 6

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.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Feng ZHU

Prof. Yuzong CHEN