**Background**
Aurora kinases are a family of serine/threonine kinases that play critical roles in cell cycle regulation, specifically during mitosis. Among them, Aurora B is essential for chromosome alignment, segregation, and cytokinesis. Overexpression or dysregulation of Aurora B is frequently observed in various malignancies, contributing to genomic instability and uncontrolled cell proliferation. Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer characterized by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression, making it difficult to treat with conventional hormonal therapies. Given the pivotal role of Aurora B in mitotic progression, targeting this kinase offers a promising strategy for treating TNBC and other solid tumors. In this context, we will introduce a potent Aurora B inhibitor – SP-96.
**Definition**
SP-96 is a highly potent, selective, and non-ATP-competitive Aurora B inhibitor with an IC50 value of 0.316 nM.
**In Vitro Studies**
According to the SP-96 description, this compound exhibits exceptional selectivity, showing >2000-fold selectivity against FLT3 (IC50 = 1475.6 nM) and KIT (IC50 = 1307.6 nM). In terms of SP-96 biological activity, the compound inhibits Aurora B enzymatic activity with an IC50 of 0.316 nM and Aurora A with an IC50 of 18.975 nM. It also demonstrates minimal inhibitory effects on other receptor tyrosine kinases, including EGFR, RET, and HER2, with IC50 values ≥2 μM.
In cellular assays, SP-96 (0-1 μM; 24 hours) showed selective growth inhibition across various cell lines. Specifically, it inhibited the growth of MDA-MB-468, CCRF-CEM, COLO 205, and A498 cells with GI50 values of 107 nM, 47.4 nM, 50.3 nM, and 53.2 nM, respectively. Furthermore, SP-96 (63.2 nM) was found to inhibit Aurora B activity in H460 cells, resulting in increased DNA content, increased cell volume, and the formation of enormous nuclei. These results indicate that SP-96 effectively disrupts mitotic processes, making it a valuable tool for SP-96 cancer research. In conclusion, SP-96 is a highly potent and selective non-ATP-competitive Aurora B inhibitor with significant antiproliferative activity against several cancer cell lines, including those associated with triple-negative breast cancer.
Keywords
SP-96, 2682114-54-9, SP96, SP 96, Aurora Kinase, hematopoiesis, NCI60, MDA-MD-468, Triple Negative, Breast Cancer,, Inhibitor, inhibitor, inhibit
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