CDK19 Inhibitor

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

CDK8/19-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.

MK256 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.

CDK8-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-STAT1^SER727 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%.