CDK8
CDK8 (cyclin-dependent kinase 8) is a transcription-associated kinase that functions within the Mediator kinase module and regulates RNA polymerase II-dependent gene expression through reversible association with the Mediator complex.[1][2] Mechanistically, CDK8 integrates developmental, metabolic, inflammatory, and signal-responsive transcriptional programs by modulating transcription factor activity and enhancer-driven transcriptional output.[2][3] In disease-relevant contexts, dysregulation of CDK8 signaling has been linked to multiple human disorders, particularly cancer, where Mediator kinase activity contributes to transcriptional reprogramming and tumor-promoting gene expression networks.[2][4] Experimental studies further demonstrate that CDK8 and CDK19 regulate intestinal lineage specification through Mediator-dependent control of chromatin-remodeling mechanisms and enhancer function.[5] Compared with the related isoform CDK19, CDK8 is more broadly expressed across tissues, whereas CDK19 shows greater tissue specificity; however, both kinases display highly overlapping transcriptional and phosphoregulatory functions and often act redundantly within the Mediator kinase module.[3] Therefore, genetic disruption of a single paralog frequently produces partial phenotypes, while dual inhibition more closely recapitulates Mediator kinase suppression.[3] For experimental applications, most currently reported Mediator kinase inhibitors target both CDK8 and CDK19, and these compounds are widely used to investigate transcriptional reprogramming, signal-induced gene expression, and therapeutic vulnerabilities in cancer models.[3][4]
References:
- [1]. Fant CB, et al. Regulatory functions of the Mediator kinases CDK8 and CDK19. Transcription. 2019 Apr;10(2):76-90. [Content Brief]
- [2]. Dannappel MV, et al. Molecular and in vivo Functions of the CDK8 and CDK19 Kinase Modules. Front Cell Dev Biol. 2019 Jan 14;6:171. doi: 10.3389/fcell.2018.00171. PMID: 30693281; PMCID: PMC6340071. [Content Brief]
- [3]. Chen M, et al. CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins. Nucleic Acids Res. 2023 Aug 11;51(14):7288-7313. doi: 10.1093/nar/gkad538. PMID: 37378433; PMCID: PMC10415139. [Content Brief]
- [4]. Luyties O, et al. The Mediator kinase module: an interface between cell signaling and transcription. Trends Biochem Sci. 2022 Apr;47(4):314-327. doi: 10.1016/j.tibs.2022.01.002. Epub 2022 Feb 19. PMID: 35193797; PMCID: PMC8939868. [Content Brief]
- [5]. Dannappel MV, et al. CDK8 and CDK19 regulate intestinal differentiation and homeostasis via the chromatin remodeling complex SWI/SNF. J Clin Invest. 2022 Oct 17;132(20):e158593. doi: 10.1172/JCI158593. PMID: 36006697; PMCID: PMC9566890. [Content Brief]
-
CDK8 Related Products (57)
Related Products (57)
-
LL-K8-22
0 ImagesLL-K8-22 is a dual degrader of CDK8 and cyclin C HyT, with DC50 values of 2.52 μM and 2.64 μM, respectively. LL-K8-22 inhibits phosphorylation of STAT1 Ser 727, phosphorylation of the C-terminal domain Ser 2/5 of RNA polymerase II, and phosphorylation of Rb. LL-K8-22 represses E2F- and MYC-driven transcriptional programs and exhibits antiproliferative effects. LL-K8-22 synchronously induces proteasome-dependent selective degradation of CDK8 and cyclin C without degrading CDK19, other CDK family members, or other cyclins. LL-K8-22 can be used in the research of triple-negative breast cancer and colon cancer.
-
Senexin C
0 ImagesSenexin C is a selective and orally active CDK8/19 inhibitor. Senexin C shows a strong tumor-enrichment pharmacokinetic (PK) profile and tumor-pharmacodynamic (PD) marker responses. Senexin C inhibits the growth of MV4-11 leukemia cells with good tolerability.
-
Tambiciclib dimaleate
0 ImagesSynonyms: GFH009 dimaleate; JSH-009 dimaleate; SLS009 dimaleateTambiciclib (GFH009, JSH-009) dimaleate is an orally active, highly potent and selective CDK9 inhibitor (IC50 = 1 nM), demonstrating >200-fold selectivity over other CDKs, >100-fold selectivity over DYRK1A/B, and excellent selectivity over 468 kinases/mutants. Tambiciclib dimaleate demonstrates potent in vitro and in vivo antileukemic efficacy in acute myeloid leukemia (AML) mouse models by inhibiting RNA Pol II phosphorylation, downregulating MCL1 and MYC, and inducing apoptosis. Tambiciclib dimaleate can be used for AML research.
-
P162-0948
0 ImagesP162-0948 is a selective CDK8 inhibitor with an IC50 value of 50.4 nM. P162-0948 reduces cell migration and protein expression of EMT-related proteins in A549 human alveolar epithelial cell lines. P162-0948 reduces phosphorylation of Smad, which suggests disruption of the TGF-β/Smad signaling pathway. P162-0948 is promising for research of pulmonary fibrosis.
-
CDK8-IN-12
0 ImagesCDK8-IN-12 is an orally active, potent CDK8 inhibitor with a Ki of 14 nM. CDK8-IN-12 has off-target kinase inhibition on GSK-3α, GSK-3β, PCK-θ with Kis of 13 nM, 4 nM, 109 nM, respectively. CDK8-IN-12 shows potent anti-proliferative effects selectively on MV4-11 cell. CDK8-IN-12 is an anti-cancer agent.
-
JH-VIII-49
0 ImagesCat. No.: HY-125001CAS No.: 2209084-73-9JH-VIII-49 (compound 10) is a potent and selective CDK8 inhibitor (IC50=16 nM) with excellent biological activity. JH-VIII-49 promotes CDK8 inhibition through its steroid backbone design. JH-VIII-49 can be used in the synthesis of PROTAC as a target protein ligand of JH-XI-10-02 (HY-111518).
-
Senexin A hydrochloride
0 ImagesCat. No.: HY-15681ACAS No.: 1780390-76-2Senexin A hydrochloride is an inhibitor of CDK8/19 (IC50: 280 nM, CDK8) and an inhibitor downstream of p21 transcription. It only inhibits p21-induced transcription but does not inhibit other biological effects of p21. Senexin A hydrochloride inhibits CMV-GFP induction as well as the p21 stimulatory activity of the consensus NF-κB-dependent promoters.
-
CDK8-IN-6
0 ImagesCat. No.: HY-147716CAS No.: 2415156-27-1CDK8-IN-6 (compound 9) is a potent cyclin-dependent kinase 8 (CDK8) inhibitor with an Kd of 13 nM. CDK8-IN-6 shows cytotoxicity for MOLM-13, OCI-AML3, MV4-11, NRK and H9c2 cells with IC50s of 11.2, 7.5, 8.6, 20.5, 12.5-25 µM, respectively. CDK8-IN-6 has the potential for the research of AML-cancer.
-
CDK8-IN-17
0 ImagesCat. No.: HY-169633CAS No.: 451458-32-5
-
PI3Kα-IN-26
0 ImagesCat. No.: HY-176281PI3Kα-IN-26 (Compound 11e) is a PI3Kα inhibitor with an IC50 of 75.31 nM. PI3Kα-IN-26 has a broad-spectrum anticancer activity, such as leukemia, colon and breast cancer, without significant cytotoxic effect on the normal Vero cells (mean IC50s of 2.74, 3.50, 3.34 and 85.29 μM, respectively).
