PLAGL2 inhibitor Compound C8 is a small-molecule inhibitor targeting PLAGL2 (Pleiomorphic adenoma-like protein 2) with SPR KD of 2.23 uM, inhibits PLAGL2 transcriptional activity and HCC cell viability (MHCC-97H, IC50=3.69 uM).
Compound C8 shows potent cell viability inhibition against PLAGL2 high-expressed cells ( lung cancer (IC50=0.96-1.35 μM) and breast cancer (IC50=1.64 -2.21 uM)).
Compound C8 remarkably inhibits colony formation of HCC cells (MHCC-97H, IC50=0.02 uM), reduces division of HCC cells, inhibits migration and invasion ability of HCC cells.
Compound C8 interferes with the extracellular matrix organization pathway in HCC.
Compound C8 significantly inhibits PLAGL2-dependent AKT phosphorylation at both Thr308 and Ser473, indicating its ability to suppress both the EGFR-PI3K-PDK1 and EGFR-PI3K-mTORC2 axes to exert anti-tumor effects.
Compound C8 (15 mg/kg/day, i.p.) effectively inhibited tumor growth in HCCLM3-derived subcutaneous xenograft tumor models.