YZ-35

YZ-35 is a novel, natural product-derived small molecule that functions as a potent inhibitor of Signal Transducer and Activator of Transcription 3 (STAT3). It was developed through structure-guided optimization of Juglone. YZ-35 demonstrates high affinity for STAT3 (IC50 = 190 nM) and effectively suppresses STAT3 phosphorylation. The drug exhibits remarkable antiproliferative activity across various breast cancer cell lines and selectively inhibits the self-renewal of breast cancer stem cells (BCSCs). In preclinical xenograft models, YZ-35 achieved approximately 90% tumor growth inhibition at a dose of 10 mg/kg, with a favorable toxicity profile compared to paclitaxel. Its mechanism involves disrupting the STAT3 pathway and depleting BCSCs, offering a dual antitumor and anti-cancer stem cell strategy for refractory breast cancer.