ZSTK3744

ZSTK3744 is a novel, small-molecule aryl hydrocarbon receptor (AhR) agonist developed by Zenyaku Kogyo. It exhibits potent antitumor activity against triple-negative breast cancer (TNBC) and ovarian cancer, including chemotherapy-resistant TNBC cell lines. Mechanistically, ZSTK3744 directly binds to AhR, leading to the upregulation of AhR target genes such as CYP1A1, CYP1B1, and TIPARP, which induces reactive oxygen species (ROS) generation, DNA damage, and apoptosis. Unlike earlier AhR agonists like aminoflavone (and its prodrug AFP464) which are associated with severe pulmonary toxicity, ZSTK3744 has demonstrated a favorable safety profile with no evidence of lung toxicity in preclinical dog models.