CDK8 Inhibitor

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

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

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.

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.

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.

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.

SNX631 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. The combination of SNX631 with Lapatinib (HY-50898) or Trastuzumab (HY-P9907) synergistically inhibits cancer cell growth, upregulates the tumor suppressor BTG2 and prevents Lapatinib-induced upregulation of oncogenic miRNAs. SNX631 partially inhibits tumor growth; when combined with Lapatinib, it significantly suppresses tumors and 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.

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.

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

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.

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.

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

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.

DS96432529 is an orally active CDK8 inhibitor with an IC₅₀ of 33 nM. DS96432529 enhances ALPase activity, with an EC₂₀₀ of 63 nM. DS96432529 inhibits TNF-α-induced activation of the RLR signaling pathway, activates mitophagy, accelerates mineralized nodule formation, and suppresses the proliferation of periodontal ligament stem cells. DS96432529 promotes bone formation, alleviates ligation-induced alveolar bone loss, and increases bone mineral density in ovariectomized animal models. DS96432529 can be used in studies related to periodontitis and osteoporosis.

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

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-XI-10-02 is a PROTAC connected by ligands for Cereblon and CDK. JH-XI-10-02 is a highly potent and selective PROTAC CDK8 degrader, with an IC₅₀ of 159 nM. JH-XI-10-02 causes proteasomal degradation, does not affect CDK8 mRNA levels. JH-XI-10-02 shows no effect on CDK19.