| In Vitro |
CDK8-IN-11 (compound 29, 200 nM) shows inhibitory effects against CDK8 by 73.6% [1]. CDK8-IN-11 (0-50 μM, 48 h) inhibits cell proliferation in HCT-116, HHT-29, SW480, CT-26, GES-1 cells [1]. CDK8-IN-11 (0-4 μM, 48 h) inhibits the phosphorylation of STAT1 at Ser727 mediated by CDK8 in HCT-116 cells [1]. CDK8-IN-11 (0-4 μM, 24 h) suppresses canonical WNT/β-catenin signaling pathways and deregulates β-catenin-mediated transcription in HCT-116 cells [1]. CDK8-IN-11 (0.5-2 μM, 48 h) increases the number of cells in the G1 phase in HCT-116 cells [1]. CDK8-IN-11 (0-4 μM) reverses Sorafenib resistance of HCT-116 cells [1]. Cell Proliferation Assay [1] Cell Line: HCT-116, HHT-29, SW480, CT-26, GES-1 cells Concentration: 0.08, 0.4, 2, 10, and 50 μM Incubation Time: 48 h Result: Inhibited cell proliferation with IC 50 values of 1.2, 0.7, 2.4, 5.5, 62.7 nM respectively. Western Blot Analysis [1] Cell Line: HCT-116 cell Concentration: 0, 1, 2, 4 μM Incubation Time: 48 h Result: Inhibited the phosphorylation of STAT1 at Ser727 without affecting the JAK-regulated phosphorylation at Tyr701. Cell Cycle Analysis [1] Cell Line: HCT-116 cell Concentration: 0.5-2 μM Incubation Time: 48 h Result: Increased the number of cells in the G1 phase with an obvious decreased percentage of cells in the G2/M and S phase in HCT-116 cells.
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| In Vivo |
CDK8-IN-11 (compound 29, 10 and 40 mg/kg, p.o.) inhibits tumor growth in CT-26 xenograft mice [1]. CDK8-IN-11 (1000 mg/kg, oral gavage, ICR mice) shows no obvious abnormal behavior within 7 days [1]. CDK8-IN-11 (10 mg/kg, p.o.; 2 mg/kg, i.v., rats) shows moderate permeability with an apparent permeability coefficient value of 1.8 × 10 6 cm/s [1]. Animal Model: CT-26 xenograft mice [1] Dosage: 10 and 40 mg/kg Administration: Oral adminstration (p.o.) Result: Reduced the tumor volume, reduced β-catenin and c-Myc level in tumor. Animal Model: Rats (pharmacokinetic assay) [1] Dosage: 10 mg/kg (p.o.), 2 mg/kg (i.v.) Administration: Oral adminstration (p.o.) or intravenous injection (i.v.) Result: Pharmacokinetic profile of CDK8-IN-11 (compound 29). dose (mg/kg) T 1/2 (h) T max (h) C max (ng/mL) F (%) 10 (p.o.) 1.1 0.8 453 31.7 2 (i.v.) 0.5 318
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