CDK19
CDK19 is an alternative enzymatic component of the Mediator kinase module, which contains CDK8 or CDK19, cyclin C, MED12, and MED13 and regulates RNA polymerase II-linked transcriptional programs[1]. Mechanistically, CDK8/19 support signal-induced transcription, including NF-κB-induced transcriptional elongation and expression of IL8, CXCL1, and CXCL2[2]. In intestinal models, CDK8 and CDK19 redundantly regulate lineage specification through SWI/SNF phosphorylation and enhancer colocalization[3]. In hematopoietic and acute myeloid leukemia models, CDK19 regulates proliferation through the p53-p21 pathway[4]. Compared with CDK8, CDK19 shows context-dependent distinction: in the IFN-γ pathway, CDK8 acts through kinase activity, whereas CDK19 functions as a scaffold and regulates different gene sets[5]. However, broader transcriptomic, proteomic, and phosphoproteomic analyses found qualitatively similar CDK8 and CDK19 effects, with differences mainly reflecting expression and activity levels[1]. For experimental applications, selective CDK8/19 inhibitors, PROTAC degraders, and genetic perturbation help define Mediator kinase activity, transcriptional reprogramming, STAT phosphorylation, and therapy-response mechanisms[1][6][7].
References:
- [1]. 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. [Content Brief]
- [2]. Chen M, et al. CDK8/19 Mediator kinases potentiate induction of transcription by NFκB. Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10208-10213. [Content Brief]
- [3]. 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. [Content Brief]
- [4]. Zhang Z, et al. CDK19 regulates the proliferation of hematopoietic stem cells and acute myeloid leukemia cells by suppressing p53-mediated transcription of p21. Leukemia. 2022 Apr;36(4):956-969. [Content Brief]
- [5]. Steinparzer I, et al. Transcriptional Responses to IFN-γ Require Mediator Kinase-Dependent Pause Release and Mechanistically Distinct CDK8 and CDK19 Functions. Mol Cell. 2019 Nov 7;76(3):485-499.e8. [Content Brief]
- [6]. Liao JZ, et al. Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila. Nat Commun. 2024 Apr 18;15(1):3326. [Content Brief]
- [7]. Ding X, et al. Inhibition of CDK8/19 Mediator kinase potentiates HER2-targeting drugs and bypasses resistance to these agents in vitro and in vivo. Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2201073119. [Content Brief]
All Product Categories
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CDK19 Related Products (25)
Related Products (25)
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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%.
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