CDK8 Inhibitor

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-IN-13 is a potent, selective and orally active CDK8 inhibitor with an IC₅₀ value of 51.9 nM. CDK8-IN-13 induces apoptosis. CDK8-IN-13 decreases the expression of p-STAT1 S727 and p-STAT5 S726. CDK8-IN-13 shows antitumor activity.

CDK8-IN-11 is a potent and selective CDK8 inhibitor with an IC₅₀ value of 46 nM. CDK8-IN-11 inhibits WNT/β-catenin signaling pathway. CDK8-IN-11 can be used in the research of colon cancer.

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.

Tambiciclib (GFH009, JSH-009) dimaleate 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 dimaleate 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 dimaleate can be used for AML research.

P162-0948 is a selective CDK8 inhibitor with an IC₅₀ value of 50.4 nM. P162-0948 reduces cell migration and protein expression of EMT-related proteins in A549 human alveolar epithelial cell lines. P162-0948 reduces phosphorylation of Smad, which suggests disruption of the TGF-β/Smad signaling pathway. P162-0948 is promising for research of pulmonary fibrosis.

CDK8-IN-1 is a potent and selective CDK8 inhibitor with an IC₅₀ of 3 nM.

CDK8-IN-12 is an orally active, potent CDK8 inhibitor with a K_i of 14 nM. CDK8-IN-12 has off-target kinase inhibition on GSK-3α, GSK-3β, PCK-θ with K_is of 13 nM, 4 nM, 109 nM, respectively. CDK8-IN-12 shows potent anti-proliferative effects selectively on MV4-11 cell. CDK8-IN-12 is an anti-cancer agent.

JH-VIII-49 (compound 10) is a potent and selective CDK8 inhibitor (IC₅₀=16 nM) with excellent biological activity. JH-VIII-49 promotes CDK8 inhibition through its steroid backbone design. JH-VIII-49 can be used in the synthesis of PROTAC as a target protein ligand of JH-XI-10-02 (HY-111518).

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-IN-6 (compound 9) is a potent cyclin-dependent kinase 8 (CDK8) inhibitor with an K_d of 13 nM. CDK8-IN-6 shows cytotoxicity for MOLM-13, OCI-AML3, MV4-11, NRK and H9c2 cells with IC₅₀s of 11.2, 7.5, 8.6, 20.5, 12.5-25 µM, respectively. CDK8-IN-6 has the potential for the research of AML-cancer.

CDK8-IN-17 (Compound WS-2) is a CDK8 inhibitor with an IC₅₀ value of 9 nM, which can be used in cancer research.

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).

PI3Kα-IN-26 (Compound 11e) is a PI3Kα inhibitor with an IC₅₀ of 75.31 nM. PI3Kα-IN-26 has a broad-spectrum anticancer activity, such as leukemia, colon and breast cancer, without significant cytotoxic effect on the normal Vero cells (mean IC₅₀s of 2.74, 3.50, 3.34 and 85.29 μM, respectively).

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.

CDK8-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.

CDK8-IN-7 (compound 12) is a potent and selective cyclin-dependent kinase 8 (CDK8) inhibitor with an K_d 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.

CDK8-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.