YM-155 Hydrochloride: A Potent Survivin Inhibitor for Cancer Research

Executive Summary: YM-155 hydrochloride is a selective small-molecule inhibitor of the apoptosis protein survivin, exhibiting an IC50 of 0.54 nM in survivin suppression (ApexBio A3947). This compound shows negligible effects on other IAP family and BCL-2 related proteins, ensuring high target specificity (Schwartz 2022). YM-155 hydrochloride induces robust tumor regression in xenograft models of various cancers, including NSCLC and TNBC, and impedes spontaneous metastasis in animal models. The compound is stable as a solid at -20°C and is highly soluble in DMSO, ethanol, or water under specified conditions. Its use is restricted to scientific research and is not approved for diagnostic or therapeutic applications.

Biological Rationale

Survivin is a unique member of the inhibitor of apoptosis (IAP) family, encoded by the BIRC5 gene, and is highly expressed in most cancers but minimally in differentiated adult tissues (Schwartz 2022). Survivin plays dual roles in inhibiting apoptosis and regulating cell division. Elevated survivin expression correlates with poor prognosis and resistance to chemotherapy in cancer patients. Targeting survivin disrupts cancer cell survival mechanisms without significantly impacting normal cells, providing a rationale for its inhibition in oncology research. This selectivity underpins the value of small-molecule survivin inhibitors such as YM-155 hydrochloride.

Mechanism of Action of YM-155 Hydrochloride

YM-155 hydrochloride is a synthetic imidazolium-based molecule with the chemical formula C20H19ClN4O3 and a molecular weight of 398.84 g/mol (ApexBio). It selectively inhibits survivin at sub-nanomolar concentrations, with an IC50 of 0.54 nM in cell-based assays. YM-155 binds directly or indirectly to elements regulating survivin gene expression, suppressing survivin transcription and translation. This leads to increased caspase activation, promotion of apoptosis, and decreased cellular proliferation in cancer cell lines. The compound does not significantly inhibit other IAPs or BCL-2 family proteins, reducing potential off-target effects (Schwartz 2022).

Evidence & Benchmarks

• YM-155 hydrochloride suppresses survivin expression in vitro with an IC50 of 0.54 nM in cancer cell lines (product page).
• It has minimal activity against other IAP family members or BCL-2 proteins, indicating high specificity (Schwartz 2022, Table 2.3).
• YM-155 induces tumor regression in xenograft models, including NSCLC, melanoma, bladder cancer, aggressive non-Hodgkin lymphoma, and breast cancer (Schwartz 2022, Fig. 3.5).
• In triple-negative breast cancer (TNBC) models, YM-155 reduces spontaneous metastases and significantly prolongs animal survival (Schwartz 2022, Sec. 4.2).
• The compound maintains stability when stored at -20°C and dissolves at ≥19.45 mg/mL in DMSO, ≥4.34 mg/mL in ethanol (with warming/ultrasound), and ≥48.1 mg/mL in water (with ultrasound) (product page).

Applications, Limits & Misconceptions

YM-155 hydrochloride is widely used in preclinical studies for interrogating the role of survivin in cancer cell survival and resistance mechanisms. Its high specificity for survivin makes it a preferred tool in apoptosis inhibitor research and in evaluating the therapeutic potential of survivin-targeted therapies. The compound is particularly valuable in studies of tumor regression in xenograft and metastatic models, especially for challenging subtypes such as triple-negative breast cancer. Researchers must note that YM-155 hydrochloride is not approved for human therapeutic use and should not be used in diagnostic or clinical applications. For a deeper understanding of apoptosis inhibitor selectivity, see our review on BIRC5 Inhibitors Overview, which this article updates by focusing on the practical integration and benchmark data for YM-155 hydrochloride.

Common Pitfalls or Misconceptions

• YM-155 hydrochloride is not effective against all apoptosis-related proteins; its activity is highly selective for survivin.
• The compound should not be used as a diagnostic or therapeutic agent in humans.
• Short-term solutions are recommended; prolonged storage in solution decreases compound stability and activity.
• Off-target effects may occur at concentrations much higher than recommended; adherence to IC50-guided dosing is essential.
• Some cancer cell lines with low survivin expression may show limited response to YM-155.

Workflow Integration & Parameters

YM-155 hydrochloride is supplied as a solid and should be stored at -20°C. For in vitro use, it is soluble at ≥19.45 mg/mL in DMSO, at ≥4.34 mg/mL in ethanol with gentle warming and ultrasonic treatment, and at ≥48.1 mg/mL in water with ultrasonic treatment. Prepare solutions fresh or store short-term at recommended conditions to maximize stability. Typical in vitro studies apply YM-155 at nanomolar concentrations, guided by the target cell line’s survivin expression and documented IC50 values. The compound integrates seamlessly into apoptosis assays, proliferation studies, and xenograft model workflows. For practical tips on integrating apoptosis inhibitors into cancer biology screens, refer to our guide on Apoptosis Inhibitor Screening, which this article extends by providing survivin-specific dosing and solubility parameters.

Conclusion & Outlook

YM-155 hydrochloride is a benchmark, potent, and selective small-molecule survivin inhibitor for cancer research. Its robust activity, high specificity, and ease of integration into standard oncology research assays make it a valuable reagent for dissecting the role of the inhibitor of apoptosis protein (IAP) pathway. Future work will clarify its translational potential and further optimize survivin-targeted research tools. For product details or ordering, consult the YM-155 hydrochloride A3947 kit page.

For broader context on how survivin inhibitors fit into targeted cancer therapy research, see our comparison at Targeted Therapy Tools; this article provides detailed IC50 and workflow data specific to YM-155 hydrochloride that is not covered elsewhere.