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 (51):

By Type:	Pan (24) Selective (17)
By Effects:	Inhibitors (48) Degraders (3)

Cat. No.	Product Name	Effect	Purity

HY-N0400

Wogonin	Inhibitor	99.83%
Wogonin is a naturally occurring mono-flavonoid, can inhibit the activity of CDK8 and Wnt, and exhibits anti-inflammatory and anti-tumor effects.

HY-120350

BI-1347	Inhibitor	99.85%
BI-1347 is an orally active, selective and potent CDK8 inhibitor (IC₅₀=1.1 nM). BI-1347 shows anti-tumoral activity.

HY-126675A

AS2863619	Inhibitor	98.02%
AS2863619 is an orally active CDK8/19 inhibitor that also inhibits BMP2, MDA5 and RIG-I receptors. AS2863619 targets Stat5a-CDK8/19 to promote the differentiation of CD4⁺ T cells into regulatory T cells and induce FOXP3 expression, thereby restoring immune homeostasis and establishing transplant immune tolerance. AS2863619 also enhances the BMP2/SMAD signaling pathway to promote osteogenic differentiation and inhibit adipogenic differentiation. AS2863619 exerts osteoprotective effects by alleviating inflammation-induced impairment of osteogenic function and inducing neutrophil apoptosis (apoptosis). AS2863619 can be applied to research in related fields such as periodontitis-induced bone defects.

HY-X0009

Tambiciclib	Inhibitor	99.68%
Tambiciclib (GFH009, JSH-009) 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 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 can be used for AML research.

HY-111388A

Romaciclib monohydrochloride	Inhibitor	99.29%
SEL120-34A monohydrochloride is an ATP-competitive and selective CDK8 inhibitor, inhibits kinase activities of CDK8/CycC and CDK19/CycC complexes with IC₅₀s of 4.4 nM and 10.4 nM, respectively, with a K_d of 3 nM for CDK8. SEL120-34A monohydrochloride weakly inhibits CDK9 (calculated IC₅₀=1070 nM), but shows no obvious activity against CDK1, 2, 4, 6, 5, 7. SEL120-34A monohydrochloride inhibits phosphorylation of STAT1 S727 and STAT5 S726. Has anti-tumor activity.

HY-114178

CDK8-IN-2	Inhibitor
CDK8-IN-2 is an orally active CDK8 inhibitor of an IC₅₀ values of 0.010 μM. CDK8-IN-2 shows a CDK19 IC₅₀ value of 0.026 μM. CDK8-IN-2 inhibits phospho-STAT1, a pharmacodynamic biomarker of CDK8. CDK8-IN-2 inhibits WNT pathway activity. CDK8-IN-2 can be used for the research of colorectal carcinoma.

HY-183074

RO8323	Inhibitor
RO8323 is an orally active, selective CDK8/CDK19 inhibitor, with an IC₅₀ of 2 nM against CDK8 and 3 nM against CDK19. RO8323 promotes regulatory T cell differentiation, inhibits effector T cell generation, reverses the Teff/Treg ratio, upregulates IL-10 production in myeloid cells, and suppresses the production of TNF-α, IL-6 and IL-12. RO8323 enhances immune reconstitution and prolongs cardiac allograft survival in a dose-dependent manner. RO8323 can be used in the research of chronic graft-versus-host disease, cardiac allograft rejection, acute graft-versus-host disease and experimental autoimmune encephalomyelitis.

HY-180124

CDK8-IN-20	Inhibitor
CDK8-IN-20 (Compound 67j) is a selective, potent and orally active type I CDK8 inhibitor with an IC₅₀ of 70.5 nM. CDK8-IN-20 shows IC₅₀ values of 147.8, 726.9 and 217.4 nM for homologous kinase CDK19, CDK7 and CDK9. CDK8-IN-20 can inhibit the Wnt/β-catenin pathway and downregulate the expression of β-catenin, Cyclin D1, and c-Myc. CDK8-IN-20 can induce ROS production and cause G2/M and S phase arrest. CDK8-IN-20can be used for the research of cancer, such as colon cancer.

HY-101800

Senexin B	Inhibitor	99.09%
Senexin B (SNX2-1-165; BCD-115) is a potent, highly water-soluble and bioavailable CDK8/19 inhibitor, with K_ds of 140 nM for CDK8 and 80 nM for CDK19.

HY-15681

Senexin A	Inhibitor	99.58%
Senexin A 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 inhibits CMV-GFP induction as well as the p21 stimulatory activity of the consensus NF-κB-dependent promoters.

HY-101611

MSC2530818	Inhibitor	99.62%
MSC2530818 is a potent, selective and orally available CDK8 inhibitor with an IC₅₀ of 2.6 nM for CDK8.

HY-137478

KB-0742	Inhibitor	99.63%
KB-0742 is a potent, selective and orally active CDK9 inhibitor with an IC₅₀ of 6 nM for CDK9/cyclin T1. KB-0742 is selective for CDK9/cyclin T1 with >50-fold selectivity over other CDK kinases. KB-0742 has potent anti-tumor activity.

HY-137478A

KB-0742 dihydrochloride	Inhibitor	98.77%
KB-0742 dihydrochloride is a potent, selective and orally active CDK9 inhibitor with an IC₅₀ of 6 nM for CDK9/cyclin T1. KB-0742 dihydrochloride is selective for CDK9/cyclin T1 with >50-fold selectivity over other CDK kinases. KB-0742 dihydrochloride has potent anti-tumor activity.

HY-19984

CCT-251921	Inhibitor	99.12%
CCT-251921 is a potent, selective, and orally bioavailable CDK8 inhibitor with an IC₅₀ of 2.3 nM.

HY-111388B

Romaciclib hydrochloride	Inhibitor	99.98%
SEL120-34A hydrochloride is a potent, selective, orally available, ATP-competitive CDK8 inhibitor, with IC₅₀s of 4.4 nM and 10.4 nM for CDK8/CycC and CDK19/CycC, respectively, with antitumor activity.

HY-145121

DS96432529	Inhibitor	99.93%
DS96432529 is a potent and orally active bone anabolic agent through CDK8 inhibition.

HY-122586

BRD6989	Inhibitor	99.54%
BRD6989, an analog of the natural product cortistatin A (dCA), inhibits CDK8 and upregulates IL-10. BRD6989 selectively binds a complex of CDK8 with an IC₅₀ of ~200 nM. BRD6989 inhibits the kinase activity of recombinant CDK8 or CDK19 complexes.

HY-12280

THZ2	Inhibitor	99.03%
THZ2 is a potent and selective CDK7 inhibitor with an IC₅₀ of 13.9 nM.

HY-149209

LL-K8-22	Degrader	99.06%
LL-K8-22 is a potent, selective and durable PROTAC CDK8-cyclin C dual degrader, with DC₅₀ values of 2.52 and 2.64 μM, respectively. LL-K8-22 also suppresses STAT1 Ser 727 phosphorylation. LL-K8-22 inhibits E2F- and MYC-driven carcinogenic transcriptional programs. LL-K8-22 can be used for triplenegative breast cancer (TNBC) research.

HY-156366

SNX7886	Degrader	99.71%
SNX7886 is a CDK8/CDK19 PROTAC degrader. SNX7886 promotes the ubiquitination and degradation of CDK8 and CDK19. SNX7886 also promotes the degradation of CCNC. SNX7886 can be used in cancer research.

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