AKT1-IN-11, a derivative of Podophyllotoxin, functions as a dual inhibitor of AKT1 and tubulin. It reduces phosphorylation levels of AKT kinase in tumor cells, disrupts cell proliferation, causes G2/M phase arrest, and induces apoptosis. Additionally, AKT1-IN-11 promotes tubulin depolymerization and is applicable in colorectal cancer research.

AKT1-IN-11 (Compound 2b) inhibits proliferation of HCT-116, HT-29, HCT-8, and NCM460 cells with IC50 values of 0.77, 0.48, 1.68, and 52.28 μM, respectively. At a concentration of 0.2 μM for 12-24 hours, AKT1-IN-11 induces apoptosis in HCT-116 cells. It also inhibits the migration of HCT-116 cells and reverses the epithelial-mesenchymal transition process when applied at 0.1-0.2 μM for 24 hours. Additionally, a dose of 0.1-0.2 μM for 2-8 hours induces G2/M phase arrest in HCT-116 cells while downregulating Cyclin B1 and CDK4 expression. Furthermore, AKT1-IN-11 at 0.1 μM over a period of 12 hours promotes microtubule depolymerization in HCT-116 cells. At 0.1-0.2 μM for 24 hours, it downregulates p-AKT expression in a concentration-dependent manner, thereby inhibiting AKT pathway activation.

Compound AKT1-IN-11 (Compound 2b), administered via intraperitoneal injection at a dose of 1-2 mg/kg every other day for a total of six doses, significantly inhibited tumor growth in a mouse xenograft model of HCT-116.