LL-K8-22

LL-K8-22 (0.38-12 μM; 0-72 h) induces dose-dependent, proteasome-mediated, simultaneous, and durable degradation of CDK8 and cyclin C (with DC₅₀ values of 2.52 μM and 2.64 μM, respectively) in MDA-MB-468 cells, with high selectivity over other CDK and cyclin family members, and exerts more significant and sustained inhibition of CDK8 downstream signaling than BI-1347^[1].
LL-K8-22 (0.625-10 μM; 0-72 h) induces effective, dose-dependent, simultaneous, and durable degradation of CDK8 and cyclin C in HCT-116 and MDA-MB-231 cells, with no hook effect^[1].
LL-K8-22 (1.1-10 μM) does not alter CDK8 or cyclin C mRNA levels but downregulates CDK1 mRNA levels in MDA-MB-468 cells^[1].
LL-K8-22 (5 μM; 12 h) selectively reduces CDK8 and cyclin C protein levels (without affecting CDK19) and downregulates CDK8 downstream targets in MDA-MB-468 cells, with affected proteins enriched in cancer-relevant pathways^[1].
LL-K8-22 binds to the CDK8-cyclin C complex such that its hydrophobic tag occupies a positively charged cavity on CDK8, potentially destabilizing the complex to enable degradation^[1].
LL-K8-22 (Gradient concentrations; 4 days) is 4.61- to 5.61-fold more potent than BI-1347 at inhibiting proliferation of MDA-MB-468, HCT-116, and MDA-MB-231 cells, with IC₅₀ values ranging from 5.73 μM to 6.22 μM^[1].
LL-K8-22 (5-20 μM; up to 5 days) exerts greater anti-proliferative effects on MDA-MB-468 cells than BI-1347 over a 5-day period at concentrations of 5, 10, and 20 μM^[1].
LL-K8-22 (1.25-20 μM; 3 weeks) potently inhibits colony formation of MDA-MB-468 cells at concentrations from 1.25 to 20 μM, with greater activity than BI-1347^[1].
LL-K8-22 (4 μM; 24 h) represses E2F- and MYC-driven carcinogenic transcriptional programs and downregulates cancer-associated genes more significantly than BI-1347 in MDA-MB-468 cells, without altering CDK8 or cyclin C mRNA levels^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.