PLAGL2-IN-1 is an inhibitor of pleomorphic adenoma gene-like 2 (PLAGL2) with a dissociation constant (Kd) of 2.23 µM. This compound suppresses the transcriptional activity of PLAGL2, induces G0/G1 cell cycle arrest and apoptosis, thereby inhibiting the proliferation of hepatocellular carcinoma (HCC) cells. It disrupts extracellular matrix structure and inhibits the PI3K-AKT signaling pathway by reducing AKT phosphorylation levels. Additionally, PLAGL2-IN-1 inhibits tumor growth in HCCLM3 xenograft mouse models and is applicable for research in hepatocellular carcinoma.

PLAGL2:2.23 μM (Kd)

PLAGL2-IN-1 (compound C8) demonstrates a broad-spectrum antiproliferative effect across various cancer cell lines with IC50 values as follows: 0.96 μM (A549), 1.35 μM (NCI-H1650), 1.03 μM (NCI-H460), 3.31 μM (MGC803), 3.28 μM (HGC27), 7.63 μM (SW620), 0.92 μM (HT29), 1.64 μM (MDA-MB-231), 2.21 μM (HCC1937), 1.43 μM (U87-MG), 24.96 μM (LN229), 8.83 μM (U937), 5.67 μM (K562), 5.33 μM (MEG01), 19.54 μM (Jurkat), 4.14 μM (PC-3), and 16.19 μM (SKOV3). At concentrations of 0-1 μM over 14 days, it inhibits colony formation in MHCC-97H and HCCLM3 cells in a concentration-dependent manner. When used at 10 μM for 48 hours, it induces apoptosis in MHCC-97H and HCCLM3 cells. At a concentration of 5 μM for 24 hours, it causes G0/G1 phase arrest in MHCC-97H cells. In the range of 0-10 μM over 48 hours, it dose-dependently inhibits the migration and invasion of HCCLM3 and MHCC-97H cells and significantly hampers cell division in HCCLM3 liver cancer cells. Furthermore, at 5-10 μM over 24-48 hours, it disrupts extracellular matrix organization in HCCLM3 cells and inhibits the PI3K-AKT pathway by reducing AKT phosphorylation.

PLAGL2-IN-1 (compound C8) at a dosage of 15 mg/kg, administered via intraperitoneal injection once daily for 19 days, significantly inhibited tumor growth in an HCCLM3 xenograft mouse model, with no noticeable toxicity.