CDK8-IN-2

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^[1]. In Vitro:CDK8-IN-2 (Compound 18) potently inhibits purified CDK8/Cyclin C protein with an IC₅₀ of 10 nM in a FRET-based binding assay^[1].
CDK8-IN-2 inhibits purified CDK8/Cyclin C protein with an IC₅₀ of 53 nM in a reporter displacement binding assay^[1].
CDK8-IN-2 inhibits purified CDK19/Cyclin C protein with an IC₅₀ of 26 nM in a reporter displacement binding assay^[1].
CDK8-IN-2 inhibits WNT pathway activity in the 7dF3 reporter cell line with an IC₅₀ of 65 nM^[1].
CDK8-IN-2 inhibits constitutive WNT pathway activity in LS174T human colorectal cancer cells with an IC₅₀ of 340 nM^[1].
CDK8-IN-2 inhibits WNT ligand-dependent WNT pathway activity in PA-1 human teratocarcinoma cells with an IC₅₀ of 710 nM^[1].
CDK8-IN-2 (4 μM) does not inhibit HSP90 in a biochemical filter assay^[1].
CDK8-IN-2 inhibits the 5HT₂A receptor with an IC₅₀ of 240 nM and shows no other significant activity against 54 additional receptors, ion channels, or enzymes at 1 μM^[1].
CDK8-IN-2 weakly inhibits PASK kinase with an IC₅₀ of 260 nM and shows no other significant activity against 306 additional kinases at 1 μM^[1].
CDK8-IN-2 inhibits the CDK8 biomarker phospho-STAT1^SER727 in SW620 human colorectal carcinoma cells with a free-plasma corrected IC₅₀ of 49 nM^[1]. In Vivo:CDK8-IN-2 (Compound 18) (20 mg/kg, p.o., single dose) inhibits phospho-STAT1^SER727 levels in an APC-mutant SW620 human colorectal carcinoma xenograft mouse model[1].