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]

CDK19 Related Products (22):

By Type:	Pan (13) Selective (4)
By Effects:	Inhibitors (19) Degraders (2)

Cat. No.	Product Name	Effect	Purity

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-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-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-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-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-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-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-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.

HY-126675

AS2863619 free base	Inhibitor	99.87%
AS2863619 free base is an orally active CDK8/19 inhibitor that also inhibits BMP2, MDA5 and RIG-I receptors. AS2863619 free base 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 free base also enhances the BMP2/SMAD signaling pathway to promote osteogenic differentiation and inhibit adipogenic differentiation. AS2863619 free base exerts osteoprotective effects by alleviating inflammation-induced impairment of osteogenic function and inducing neutrophil apoptosis (apoptosis). AS2863619 free base can be applied to research in related fields such as periodontitis-induced bone defects.

HY-139875

JH-XVI-178	Inhibitor	98.87%
JH-XVI-178 is a highly efficient and selective CDK8/19 inhibitor, with IC₅₀ values of 1 and 2 nM for CDK8 and CDK19, respectively. JH-XVI-178 has a low clearance rate and moderate oral pharmacokinetic properties.

HY-143889

Senexin C	Inhibitor	99.19%
Senexin 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.

HY-168683

CDK8 ligand 1	Degrader	99.88%
CDK8 ligand 1 is the ligand of CDK8. CDK8 ligand 1 can be used to synthesize LL-K8-22 (HY-149209).

HY-111427

CDK8/19-IN-1	Inhibitor	98.08%
CDK8/19-IN-1 is a potent, selective and oral bioavailable CDK8/19 dual inhibitor, with IC₅₀s of 0.46 nM, 0.99 nM and 270 nM for CDK8, CDK19 and CDK9, respectively.

HY-111388

SEL120-34A	Inhibitor	99.49%
SEL120-34A 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-15681A

Senexin A hydrochloride	Inhibitor
Senexin 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.

HY-168846

CDK8/19-IN-3	Inhibitor
CDK8/19-IN-3 (compound 3-7) is a potent and selective CDK8 and CDK19 inhibitor. CDK8/19-IN-3 upregulates IL-10 levels. CDK8/19-IN-3 has the potential for the research of inflammatory bowel disease (IBD).

HY-D2311

CDK19 Probe 1
CDK19 Probe 1 (Compound 10c) is a CDK19 inhibitor (IC₅₀: 1.01 μM) and can be used for cancer research.

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