Identification of a small-molecule targeting PLAGL2 DNA-binding domain inhibits extracellular matrix formation and enhances lenvatinib sensitivity in hepatocellular carcinoma - PubMed
8 hours ago
- #hepatocellular carcinoma
- #PLAGL2 inhibitor
- #extracellular matrix
- The study focuses on targeting PLAGL2 in hepatocellular carcinoma (HCC) to inhibit extracellular matrix (ECM) remodeling and enhance sensitivity to lenvatinib.
- PLAGL2 promotes ECM remodeling via autocrine and paracrine mechanisms, regulating IGF2 and IGF1R, which activate the IGF1R-PI3K-Akt pathway.
- A novel compound, DC218, derived from cytisine, was developed as a specific inhibitor of the PLAGL2 DNA binding domain using computer-aided drug design.
- DC218 significantly degrades ECM, overcomes lenvatinib resistance, and synergistically inhibits HCC progression.
- The findings provide insights into PLAGL2's role in HCC ECM remodeling and propose a new therapeutic strategy for HCC treatment.