General Information of the Protein
Protein ID
PT01476
Protein Name
Mitogen-activated protein kinase kinase kinase 8
Secondarily
Protein Name
Cancer Osaka thyroid oncogene
Proto-oncogene c-Cot
Serine/threonine-protein kinase cot
Tumor progression locus 2
Gene Name
MAP3K8
Secondarily
Gene Name
COT
ESTF
Sequence
MEYMSTGSDNKEEIDLLIKHLNVSDVIDIMENLYASEEPAVYEPSLMTMCQDSNQNDERSKSLLLSGQEVPWLSSVRYGTVEDLLAFANHISNTAKHFYGQRPQESGILLNMVITPQNGRYQIDSDVLLIPWKLTYRNIGSDFIPRGAFGKVYLAQDIKTKKRMACKLIPVDQFKPSDVEIQACFRHENIAELYGAVLWGETVHLFMEAGEGGSVLEKLESCGPMREFEIIWVTKHVLKGLDFLHSKKVIHHDIKPSNIVFMSTKAVLVDFGLSVQMTEDVYFPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAYPSYLYIIHKQAPPLEDIADDCSPGMRELIEASLERNPNHRPRAADLLKHEALNPPREDQPRCQSLDSALLERKRLLSRKELELPENIADSSCTGSTEESEMLKRQRSLYIDLGALAGYFNLVRGPPTLEYG
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
STE protein kinase group
>
STE protein kinase STE11 family
Function
Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.
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Uniprot ID
Primary ID:
P41279

Secondarily ID:
A8K2Q5
D3DRX1
Q14275
Q5T855
Q9HC81
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Ensembl ID
ENSG00000107968
HGNC ID
HGNC:6860
Subcellular Location
Cytoplasm
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000013 , Sf9
Compound ID Compound Name Compound Formula
CP0006184
6,7,13,14-tetrahydroxy-2,9-dioxatetracyclo[6.6.2.0^{4,16}.0^{11,15}]hexadeca-1(14),4(16),5,7,11(15),12-hexaene-3,10-dione
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C14H6O8
 1
1
IC50 = 2370 nM
   TI
   LI
   LO
   TS
CP0009041
5-propan-2-yl-7,8-dihydro-6H-indeno[1,2-b]indole-9,10-dione
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C18H17NO2
 1
1
IC50 > 35000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0225027
N-[(2R)-1-morpholin-4-ylpropan-2-yl]-6-(8-pyridin-4-ylimidazo[4,5-c][1,7]naphthyridin-1-yl)quinolin-2-amine
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C30H28N8O
 1
1 IC50 = 30 nM
CP0203515
N-(1-morpholin-4-ylpropan-2-yl)-6-(8-pyridin-4-ylimidazo[4,5-c][1,7]naphthyridin-1-yl)quinolin-2-amine
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C30H28N8O
 1
1 IC50 = 60 nM
CP0300594
N-(1-morpholin-4-ylpropan-2-yl)-6-(8-pyridin-4-ylimidazo[4,5-c][1,7]naphthyridin-1-yl)-1,3-benzothiazol-2-amine
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C28H26N8OS
 2
1 IC50 = 70 nM
2 IC50 = 80 nM
CP0300593
N-(1-morpholin-4-ylpropan-2-yl)-6-(8-phenylimidazo[4,5-c][1,7]naphthyridin-1-yl)-1,3-benzothiazol-2-amine
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C29H27N7OS
 2
1 IC50 = 120 nM
2 IC50 = 130 nM
CP0300592
N-(2-morpholin-4-ylethyl)-6-(8-phenylimidazo[4,5-c][1,7]naphthyridin-1-yl)-1,3-benzothiazol-2-amine
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C28H25N7OS
 2
1 IC50 = 270 nM
2 IC50 = 280 nM
CP0179259
N-(1-morpholin-4-ylpropan-2-yl)-6-(8-thiophen-2-ylimidazo[4,5-c][1,7]naphthyridin-1-yl)-1,3-benzothiazol-2-amine
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C27H25N7OS2
 2
1 IC50 = 280 nM
2 IC50 = 290 nM
CP0229225
1-quinolin-6-yl-8-thiophen-3-ylimidazo[4,5-c][1,7]naphthyridine
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C22H13N5S
 2
1 IC50 = 440 nM
2 IC50 = 540 nM
CP0321384
N-[(2S)-1-morpholin-4-ylpropan-2-yl]-6-(8-pyridin-4-ylimidazo[4,5-c][1,7]naphthyridin-1-yl)quinolin-2-amine
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C30H28N8O
 2
1 IC50 = 620 nM
2 IC50 = 1250 nM
Clinical Information about the Protein
Target 1 ( Cot oncogene messenger RNA (MAP3K8 mRNA) )
Target Type Literature-reported Target
Target 2 ( Serine/threonine-protein kinase cot (COT) )
Target Type Clinical trial Target