cdk8-in-1

CDK8-IN-1 is a selective CDK8 inhibitor (IC50: 3 nM).

CDK8-IN-12 is a selective, potent and orally active inhibitor of CDK8 (Ki: 14 nM) and is an anti-cancer agent. CDK8-IN-12 inhibits GSK-3α, GSK-3β and PCK-θ with Ki of 13 nM, 4 nM and 109 nM respectively. CDK8-IN-12 showed anti-proliferative activity against MV4-11 cells.

CDK8-IN-14 (compound 12) effectively inhibits CDK8, demonstrating an IC50 of 39.2 nM, and exhibits potent anti-AML cell proliferation effects, with a GC50 value of 0.02±0.01μM in MOLM-13 cells and 0.03±0.01μM in MV4-11 cells [1].

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

CDK8-IN-19 (Compound 3d) is a CDK8 inhibitor with an IC50 of 25.08 nM. It exhibits broad-spectrum anticancer activity, showing effectiveness against leukemia, melanoma, and breast cancer, while demonstrating no significant cytotoxicity to normal Vero cells (mean IC50 values are 2.87, 3.65, 3.79, and 45.48 μM, respectively).

CDK8-IN-11 is a selective and potent CDK8 inhibitor that shows antiproliferative activity in colon cancer cell lines, inhibiting WNT/β-catenin activation and TCF family transcriptional activity, inducing G1-phase arrest in HCT-116 cells, useful for colon cancer research.

CDK8-IN-11 hydrochloride is a selective and potent inhibitor of CDK8 (IC50: 46 nM) that inhibits the WNT/β-catenin signaling pathway and can be utilized for studying colon cancer.

CDK8-IN-10 is a selective and potent inhibitor of cell cycle protein-dependent kinase (CDK8) (IC50: 8.25 nM) that can be used to study cancer.

CDK8-IN-18, also known as ZINC584617986, is a potent and selective inhibitor of CDK8, also modulating CDK19.

CDK8-IN-13 is a CDK8 inhibitor (IC50: 51.9 nM) with potent, selective and oral activity. CDK8-IN-13 induces apoptosis and reduces the expression of p-STAT1 S727 and p-STAT5 S726. CDK8-IN-13 exhibits anti-tumour activity.

CDK8-IN-15 (Compound 46) is a potent inhibitor of CDK8, exhibiting an IC50 value of 57 nM. This compound enhances the thermal stability of CDK8 and inhibits NF-κB, while selectively targeting the CDK family and tyrosine kinases. Additionally, it actively counteracts TNF-α-induced psoriasis in vitro and boosts the expression of Foxp3 and IL-10, potentially diminishing inflammatory responses and showing promise for research into psoriasis treatments.

NU1085 is a potent poly(ADP-ribose) polymerase (PARP) inhibitors have been developed that potentiate the cytotoxicity of ionizing radiation and anticancer drugs. The biological effects of NU1085 [Ki = 6 nM], in combination with temozolomide (TM) or topotecan (TP) have been studied in 12 human tumor cell lines (lung, colon, ovary, and breast cancer). Cells were treated with increasing concentrations of TM or TP +/- NU1085 (10 microM) for 72 h.

3MB-PP1 is a bulky purine analog and a Polo-like kinase 1 (Plk1) inhibitor. In cells expressing analog-sensitive Plk1 alleles, 3MB-PP1 blocks mitotic progression and cell division arise by targeting Plk1. 3MB-PP1 specifically inhibits analog-sensitive Ssn3 (Cdk8). 3MB-PP1 inhibits Leu93 Mutant Zipper-interacting protein kinase with IC50 of 2 μM. 3MB-PP1 can be used for the research of cell division and hypha formation of Candida albicans.

CDK8/19-IN-1 is a selective, orally bioavailable dual inhibitor of CDK8 and CDK19, with IC50 values of 0.46 nM for CDK8, 0.99 nM for CDK19, and 270 nM for [CDK9].

MK256 is a novel CDK8 inhibitor that demonstrates potent antitumor activity against AML by inhibiting the STAT pathway. It induces differentiation and maturation while inhibiting proliferation in AML cell lines. MK256 decreases the phosphorylation of STAT1(S727) and STAT5(S726) and reduces mRNA expression of MCL-1 and CCL2 in these cells. Its efficacy is validated in the MOLM-14 xenograft model, showing phosphorylation inhibition of STAT1(S727) and STAT5(S726) post-treatment. Pharmacokinetic studies in the MOLM-14 model reveal a dose-dependent inhibition of the STAT pathway. Both in vitro and in vivo studies confirm that MK256 effectively downregulates the STAT pathway.

CDK8-IN-20 (Compound 67j) is a highly selective and potent type I CDK8 inhibitor with oral bioavailability, exhibiting an IC50 value of 70.5 nM. The IC50 values for its action on homologous kinases CDK19, CDK7, and CDK9 are 147.8, 726.9, and 217.4 nM, respectively. CDK8-IN-20 effectively inhibits the proliferation of HCT-116, HT-29, and SW-480 cells with IC50 values of 5.9, 17.93, and 9.52 μM, respectively, while demonstrating low cytotoxicity toward normal gastric mucosal epithelial cells (GES-1) with an IC50 greater than 100 μM. It disrupts the Wnt/β-catenin pathway, downregulating β-catenin, Cyclin D1, and c-Myc expression. Additionally, CDK8-IN-20 induces reactive oxygen species (ROS) production and leads to G2/M phase and S phase cell cycle arrest. This compound is applicable in cancer research, such as colorectal cancer.

BI-1347 is a potent, selective inhibitor of CDK8/cyclinC (IC50: 1 nM). It shows tumor growth inhibition in an in vivo xenograft model.

LL-K8-22 is a potent, selective, and durable dual degrader of CDK8-cyclin C, demonstrating DC50 values of 2.52 and 2.64 μM, respectively. This compound effectively suppresses STAT1 Ser 727 phosphorylation and inhibits carcinogenic transcriptional programs driven by E2F and MYC. LL-K8-22 is specifically utilized in research for triple-negative breast cancer (TNBC) [1].

SNX7886 is a potent PROTAC (proteolysis-targeting chimera) that effectively degrades CDK8 and CDK19, achieving 90% degradation of CDK8 and 80% degradation of CDK19 in 293 cells [1].