Related Experiment Video
Updated: Feb 1, 2026
Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
Published on: August 21, 2013
Molecular actions of sepantronium bromide (YM155) on survivin-dependent cell death in cancer and beyond
Steffanni S A Marques1, Mateus E T Oliveira1, Édipo G França-Lara1
1Graduate Program in Health Sciences, School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil.
Abstract:
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.
Insights
Sepantronium bromide (YM155) is an early small molecule that targets survivin (BIRC5) to explore cancer cell death. This review examines its mechanisms, clinical trials, and potential for new therapies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Sepantronium bromide (YM155) was developed to selectively suppress survivin (BIRC5), a protein crucial for cancer cell survival.
- Survivin regulates apoptosis and cell-cycle progression, making it a target for cancer therapy.
Purpose of the Study:
- To review the preclinical and clinical data on YM155's mechanisms of action.
- To investigate how YM155 modulates cellular processes and impacts therapy resistance.
- To discuss the challenges and future directions for survivin-targeted therapies.
Main Methods:
- Integration of preclinical research findings.
- Analysis of clinical trial data.
- Review of molecular mechanisms including transcriptional networks, mitochondrial integrity, DNA damage, and autophagy.
Main Results:
- YM155 modulates key cellular pathways but faces limitations due to adaptive redox and metabolic programs in tumors.
- Early clinical trials demonstrated a manageable safety profile but limited durable patient responses.
- Emerging evidence suggests YM155's utility beyond oncology in vascular and immune pathologies.
Conclusions:
- YM155 serves as a valuable model for understanding survivin biology and developing next-generation survivin modulators.
- Further research is needed to overcome resistance mechanisms and enhance therapeutic efficacy.
- YM155's broader applications in non-cancerous diseases warrant further investigation.
Related Concept Videos
01:18Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
02:57Surface Tension, Capillary Action, and Viscosity
The various IMFs between identical molecules of a substance are examples of cohesive forces. The molecules within a liquid are surrounded by other molecules and are attracted equally in all directions by the cohesive forces within the liquid. However, the molecules on the surface of a liquid are attracted only by about one-half as many molecules. Because of the unbalanced molecular attractions on the surface molecules, liquids contract to form a shape that minimizes the number...
01:06Fixed Action Patterns
01:41Action Potentials
01:31Action Potential
Membrane potential in neurons
Neurons typically have a resting membrane potential of about -70 millivolts (mV). When they receive...