General Information of the Protein
Protein ID
PT01975
Protein Name
Cyclin-dependent kinase 8
Secondarily
Protein Name
Cell division protein kinase 8
Mediator complex subunit CDK8
Mediator of RNA polymerase II transcription subunit CDK8
Protein kinase K35
Gene Name
CDK8
Sequence
MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGISMSACREIALLRELKHPNVISLQKVFLSHADRKVWLLFDYAEHDLWHIIKFHRASKANKKPVQLPRGMVKSLLYQILDGIHYLHANWVLHRDLKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPYHHDQLDRIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDPYFLEDPLPTSDVFAGCQIPYPKREFLTEEEPDDKGDKKNQQQQQGNNHTNGTGHPGNQDSSHTQGPPLKKVRVVPPTTTSGGLIMTSDYQRSNPHAAYPNPGPSTSQPQSSMGYSATSQQPPQYSHQTHRY
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
CMGC protein kinase group
>
CMGC protein kinase CDK family
>
CMGC protein kinase CDK8 subfamily
Function
Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation.
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Uniprot ID
Primary ID:
P49336

Secondarily ID:
Q5VUF3
Q6ISB5
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HGNC ID
HGNC:1779
Subcellular Location
Nucleus
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: CL000068 , A-549
Compound ID Compound Name Compound Formula
CP0247784
2-[(3R)-12-(4-morpholin-4-ylcyclohexyl)oxy-7-thia-9,11-diazatricyclo[6.4.0.02,6]dodeca-1(12),2(6),8,10-tetraen-3-yl]acetamide
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C21H28N4O3S
 1
1
IC50 = 22 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0018292
8-[2-amino-3-chloro-5-(1-methylindazol-5-yl)pyridin-4-yl]-2,8-diazaspiro[4.5]decan-1-one
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C21H23ClN6O
 1
1 IC50 = 2.3 nM
CP0826549
4,5-dibromo-3-methyl-1-(piperazin-1-yl)-7,8-dihydro-6H-imidazo[4,5,1-ij]quinoline hydrochloride
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C15H19Br2ClN4
 2
1 IC50 = 4.4 nM
2 IC50 = 37.2 nM
CP0137641
1-[4-chloro-3-(trifluoromethyl)phenyl]-3-(5-oxo-6-pyridin-4-ylpyrido[2,3-b][1,5]benzoxazepin-9-yl)urea
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C25H15ClF3N5O3
 1
1 IC50 = 8.25 nM
CP0257367
1-(5-oxo-6-pyridin-4-ylpyrido[2,3-b][1,5]benzoxazepin-9-yl)-3-phenylurea
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C24H17N5O3
 1
1 IC50 = 9.96 nM
CP0036099
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea
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C21H18FN5O
 2
1 IC50 = 14 nM
2 Kd = 95 nM
CP0577228
8-[3-chloro-5-(1-methylindazol-5-yl)pyridin-4-yl]-2,8-diazaspiro[4.5]decan-1-one
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C21H22ClN5O
 1
1 IC50 = 17.9 nM
CP0018477
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide
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C21H16ClF3N4O3
 5
1 IC50 = 36.6 nM
2 IC50 = 71.5 nM
3 IC50 = 185.4 nM
4 IC50 = 199 nM
5 Kd = 310 nM
CP0033258
N-[4-methyl-3-(trifluoromethyl)phenyl]-3-[3-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl]propanamide
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C24H20F3N3O
 1
1 IC50 = 46.5 nM
CP0487704
1-[6-(2-aminopyridin-4-yl)-5-oxopyrido[2,3-b][1,5]benzoxazepin-9-yl]-3-[4-chloro-3-(trifluoromethyl)phenyl]urea
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C25H16ClF3N6O3
 1
1 IC50 = 57.5 nM
CP0577227
N-(3,5-difluorophenyl)-3-[3-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl]propanamide
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C22H17F2N3O
 1
1 IC50 = 62.8 nM
CP0579865
N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[3-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl]propanamide
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C24H17F3N4O
 1
1 IC50 = 125.9 nM
CP0568659
N-(3-fluoro-4-methylphenyl)-3-[3-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl]propanamide
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C23H20FN3O
 1
1 IC50 = 158.4 nM
CP0576231
N-[4-chloro-3-(trifluoromethyl)phenyl]-3-[3-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl]propanamide
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C23H17ClF3N3O
 1
1 IC50 = 177.2 nM
CP0579864
N-(4-methylphenyl)-3-[3-(1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl]propanamide
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C23H21N3O
 1
1 IC50 = 187.6 nM
Clinical Information about the Protein
Target 1 ( Cyclin-dependent kinase 8 (CDK8) )
Target Type Clinical trial Target
Disease 3 Target-related Diseases  3
1 Acute myeloid leukaemia [ICD-11: 2A60]
2 Colorectal cancer [ICD-11: 2B91.Z]
3 Pain [ICD-11: MG30-MG3Z]
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 SEL120 Phase 1
Acute myeloid leukaemia
Investigative Drug(s) 1 Investigative Drug  1
1 Oxindole 94 Investigative
Pain
Preclinical Drug(s) 1 Preclinical Drug  1
1 CCT251545 Preclinical
Colorectal cancer