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]
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CDK8 Related Products (57)
Related Products (57)
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RO8323
0 ImagesCat. No.: HY-183074RO8323 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.
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CDK8-IN-10
0 ImagesCat. No.: HY-151371CAS No.: 2457317-40-5CDK8-IN-10 (compound 2) is a potent, selective cyclin-dependent kinase (CDK8) inhibitor with an IC50 value of 8.25 nM. CDK8-IN-10 can be used for research of cancer.
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CDK8-IN-7
0 ImagesCat. No.: HY-147717CAS No.: 2415156-30-6CDK8-IN-7 (compound 12) is a potent and selective cyclin-dependent kinase 8 (CDK8) inhibitor with an Kd of 3.5 nM. CDK8-IN-7 shows cytotoxicity for MOLM-13, OCI-AML3, MV4-11, NRK and H9c2 cells with IC50s of 5.9, 4.8, 5.4, 16.2, 12.5-25 µM, respectively. CDK8-IN-7 has the potential for the research of AML-cancer.
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CDK8-IN-5
0 ImagesCat. No.: HY-147527CAS No.: 2855087-10-2CDK8-IN-5 is a potent CDK8 inhibitor with an IC50 of 72 nM. CDK8-IN-5 shows anti-inflammatory activities with 43% IL-10 enhancement rate. CDK8-IN-5 has the potential for the research of inflammatory bowel disease.
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CDK8-IN-20
0 ImagesCat. No.: HY-180124CDK8-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.
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KB-0742 hydrochloride
0 ImagesCat. No.: HY-137478B
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CDK8-IN-19
0 ImagesCat. No.: HY-176282CDK8-IN-19 (Compound 3d) is a CDK8 inhibitor with an IC50 of 25.08 nM. CDK8-IN-19 has a broad-spectrum anticancer activity, such as leukemia, melanoma and breast cancer, without significant cytotoxic effect on the normal Vero cells (mean IC50s of 2.87, 3.65, 3.79 and 45.48 μM, respectively).
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CDK8-IN-18
0 ImagesCat. No.: HY-169541CAS No.: 642002-74-2
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SW393109
0 ImagesCat. No.: HY-187688SW393109 is a CDK8 inhibitor with an IC50 of 3.16 nM and an EC50 of 5 nM against the DKK1 reporter gene. SW393109 inhibits IFNγ-induced phosphorylation of STAT1 S727, impairs the EWSR1::FLI1 transcriptional program in Ewing sarcoma cells and suppresses tumor cell proliferation. SW393109 acts as a gain-of-function molecular trap that induces the retention of the CDK8 kinase module (CKM) and Mediator complex on chromatin. SW393109 can be used in studies related to Ewing sarcoma.
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SNX631
0 ImagesCat. No.: HY-187035CAS No.: 868066-26-6SNX631 is an orally active and selective CDK8/CDK19 inhibitor. SNX631 reduces the phosphorylation of STAT1/STAT3 S727, and upregulates miR-21-5p, miR-21-3p and miR-221 in cancer cells. SNX631 transcription-independently inhibits meiotic resumption in mouse oocytes, blocks nuclear envelope breakdown, first polar body extrusion and mitochondrial expansion and aggregation, with no cytotoxicity. SNX631, in combination with Lapatinib (HY-50898) or Trastuzumab (HY-P9907), synergistically inhibits cancer cell growth, upregulates the tumor suppressor BTG2, prevents Lapatinib-induced upregulation of oncogenic miRNAs, overcomes drug resistance, reduces the infiltration of αSMA+ stromal fibroblasts and ARG1+ M2 macrophages, and exhibits favorable biosafety. SNX631 can be used in studies related to HER2-positive breast cancer and cancer.
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CDK8-IN-15
0 ImagesCat. No.: HY-162600CAS No.: 2988020-03-5CDK8-IN-15 (Compound 46) is a potent CDK8 inhibitors with an IC50 value of 57 nM. It can enhance the thermal stability of CDK8 along with inhibition against NF-κB and have favourable selectivity across the CDK family and tyrosine kinase. Additionally, it also demostrates a positive effect in vitro psoriasis model induced by TNF-α and alleviats the inflammatory response enhancing the expression of Foxp3 and IL-10, which is promising for research of psoriasis diseases.
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LS-Q2
0 ImagesCat. No.: HY-182986LS-Q2 is a highly selective CDK4/9 inhibitor with IC50 values of 1.4 nM and 6.2 nM. LS-Q2 inhibits cancer cells proliferation, induces G2/M phase arrest, apoptosis and reduces pSer2 RNA polymerase II expression. LS-Q2 interacts synergistically with BET and Bcl-2 inhibitors to drive antitumor activity. LS-Q2 can be used for the research of cancer, such as malignant solid tumors.
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CDK8/BRD4-IN-1
0 ImagesCat. No.: HY-184727CDK8/BRD4-IN-1 is a dual CDK8/BRD4 inhibitor, with an IC50 of 5.44 μM against CDK8 and an IC50 of 4.03 μM against BRD4. CDK8/BRD4-IN-1 exhibits anticancer activity against colorectal cancer. CDK8/BRD4-IN-1 can be used for the research of colorectal cancer.
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CDK8 ligand 2
0 ImagesCat. No.: HY-184544CAS No.: 2374703-22-5
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CDK8/19-IN-2
0 ImagesCat. No.: HY-158377CAS No.: 3024381-54-9CDK8/19-IN-2 (compound 12) is an orally active and potent cyclin-dependent kinase 8/19 (CDK8 and CDK19) inhibitor, with IC50 values of 2.08 and 2.49 nM, respectively. CDK8/19-IN-2 can be used for acute myeloid leukemia (AML), breast cancer, and lymphoma research.
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MK256
0 ImagesCat. No.: HY-183423CAS No.: 2271348-04-8MK256 is an orally active, selective CDK8 inhibitor and CDK19/cyclin C inhibitor with IC50 values of 2.5 nM and 3.3 nM, respectively. MK256 downregulates phosphorylated STAT1 (S727), STAT5 (S726), MCL-1 mRNA and CCL2 mRNA. MK256 exhibits anti-tumor activity in acute myeloid leukemia. MK256 can be used for the research of acute myeloid leukemia.
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CDK8-IN-16
0 ImagesCat. No.: HY-171174CAS No.: 1860885-61-5CDK8-IN-16 (Compound 51) is an orally active dual inhibitor for CDK8 and CDK19 wih IC50 of 5.1 nM and 5.6 nM. CDK8-IN-16 inhibits the phospho-STAT1SER727 with an IC50 of 17.9 nM in SW620 cell, inhibits WNT signaling pathway with an IC50 of 7.2 nM in 7dF3 cell. CDK8-IN-16 exhibits good pharmacokinetic characteristics in rat models with an oral bioavailability of 57%.
