Molecular actions of sepantronium bromide (YM155) on survivin-dependent cell death in cancer and beyond

Sepantronium bromide (YM155) emerged as one of the earliest small molecules designed to selectively suppress survivin (BIRC5), a key regulator of apoptosis and cell-cycle progression in cancer. Over the past two decades, YM155 has provided a unique translational framework to investigate the molecular crosstalk between survivin, cellular stress responses, and therapy resistance that shape cell-death outcomes. This mini-review integrates preclinical and clinical data to delineate how YM155 modulates transcriptional networks, mitochondrial integrity, DNA damage signaling, and autophagy. Particular attention is given to adaptive redox and metabolic programs that limit its efficacy in solid and hematological tumors. The article also revisits the outcomes of early clinical trials, highlighting both the safety profile and the challenges that hindered durable patient responses. Beyond oncology, emerging findings have repositioned YM155 as a probe to interrogate survivin-regulated processes in vascular and immune pathologies. By bridging molecular and clinical evidence, this review contextualizes YM155 within the broader landscape of targeted small molecules, emphasizing its value as a model for developing next-generation survivin modulators and precision-based therapeutic strategies. • YM155 selectively suppresses survivin (BIRC5) and modulates apoptosis, autophagy, and DNA damage pathways. • Resistance arises from transporter imbalance and metabolic adaptation in tumor cells. • Clinical studies confirmed safety but limited therapeutic efficacy. • YM155 remains a translational model compound guiding next-generation survivin-targeted drug design.