cdk8 in 1

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

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].

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.

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

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.

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].

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].