Unveiling poliumoside: A herbal-derived FAK kinase inhibitor with anti-proliferative and anti-metastatic efficacy

Focal adhesion kinase (FAK) is an attractive therapeutic target overexpressed in numerous cancers. Despite extensive efforts, no FAK inhibitor has reached the market. Here, we identified poliumoside (Pol), a compound from Chinese herbs, as a novel FAK inhibitor through high-throughput virtual screening. Pol exhibited potent anti-proliferative and anti-metastatic activities both in vitro and in vivo. Mechanistically, Pol directly binds to His89 of FAK, thereby inhibiting its autophosphorylation at Y397. This inhibition led to the downregulation of the ERK-c-Myc axis, reduced transcription of IL-6, and consequent suppression of the JAK3-STAT3 signaling pathway. Our findings establish Pol as a promising FAK-targeting agent, exerting its anti-tumor effects in a FAK-dependent manner.