Target Information
Target General Information | Top | |||||
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Target ID |
T10822
(Former ID: TTDR00298)
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Target Name |
Cyclin-dependent kinase 8 (CDK8)
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Synonyms |
Protein kinase K35; Mediator of RNA polymerase II transcription subunit CDK8; Mediator complex subunit CDK8; Cell division protein kinase 8
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Gene Name |
CDK8
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Acute myeloid leukaemia [ICD-11: 2A60] | |||||
2 | Myelodysplastic syndrome [ICD-11: 2A37] | |||||
Function |
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 preinitiation 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. Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes.
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BioChemical Class |
Kinase
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UniProt ID | ||||||
EC Number |
EC 2.7.11.22
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Sequence |
MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGIS
MSACREIALLRELKHPNVISLQKVFLSHADRKVWLLFDYAEHDLWHIIKFHRASKANKKP VQLPRGMVKSLLYQILDGIHYLHANWVLHRDLKPANILVMGEGPERGRVKIADMGFARLF NSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQED IKTSNPYHHDQLDRIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKH KVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDPYFLEDPLPTSDVFAGCQIPYPKREFLT EEEPDDKGDKKNQQQQQGNNHTNGTGHPGNQDSSHTQGPPLKKVRVVPPTTTSGGLIMTS DYQRSNPHAAYPNPGPSTSQPQSSMGYSATSQQPPQYSHQTHRY Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | SEL120 | Drug Info | Phase 1 | Acute myeloid leukaemia | [2] | |
Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
1 | CCT251545 | Drug Info | Preclinical | Colorectal cancer | [3] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 6 Inhibitor drugs | + | ||||
1 | SEL120 | Drug Info | [4] | |||
2 | Macrocycle derivative 14 | Drug Info | [1] | |||
3 | Tricyclic benzimidazole derivative 1 | Drug Info | [1] | |||
4 | CCT251545 | Drug Info | [3] | |||
5 | Oxindole 16 (compound 3) | Drug Info | [5] | |||
6 | Oxindole 94 | Drug Info | [5] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"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 Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
References | Top | |||||
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REF 1 | Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70. | |||||
REF 2 | ClinicalTrials.gov (NCT04021368) SEL120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome. U.S. National Institutes of Health. | |||||
REF 3 | Kinase inhibitors: the road ahead. Nat Rev Drug Discov. 2018 May;17(5):353-377. | |||||
REF 4 | Clinical pipeline report, company report or official report of Ryvu Therapeutics. | |||||
REF 5 | Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25. |
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