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Updated: Jun 25, 2026
Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
Published on: July 30, 2020
Development and biological evaluation of a novel aurora A kinase inhibitor
Teresa Sardon1, Thomas Cottin, Jing Xu
1CRG-Cell and Developmental Biology Program, Parc de Recerca Biomedica de Barcelona, Barcelona, Spain.
Abstract:
STOP DIVIDING: In the quest for antitumorigenic compounds, aurora A kinase has recently emerged as a potential drug target. In this paper three novel aurora inhibitors (shown in the illustration) have been tested for their biological activity in cultured cells. One of them (TC-28) appears to be a promising specific aurora A inhibitor in vivo. The aurora kinase family groups several serine/threonine kinases with key regulatory functions during cell division. The three mammalian members, aurora A, B and C, are frequently over-expressed in human tumors and the aurora A gene is located in a genomic region frequently amplified in breast and colon cancer. All these data have fuelled the idea that aurora kinases are promising targets for anticancer therapy. Indeed some inhibitory compounds are currently being evaluated in clinical trials. However, it was recently shown that mutations in the targeted kinase can confer resistance to a broad range of inhibitors and render patients resistant to treatments. Moreover, aurora A over-expression results in increased resistance to antimitotic agents. The development of new compounds targeting aurora A is therefore highly relevant. We describe here the synthesis of three novel aurora kinase inhibitors, TC-28, TC-34 and TC-107. We report their properties as aurora inhibitors in vitro and their effect on human tissue culture cell lines. Interestingly, our results show that TC-28 has properties compatible with the specific inhibition of aurora A, in vivo.
Insights
Researchers developed novel aurora kinase inhibitors for cancer therapy. TC-28 shows promise as a specific aurora A inhibitor, potentially overcoming drug resistance in cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Aurora kinases are crucial for cell division and are often over-expressed in human tumors, making them attractive targets for cancer therapy.
- Over-expression of aurora A kinase is linked to increased resistance to existing cancer treatments, highlighting the need for new therapeutic strategies.
- Genetic amplification of the aurora A gene in breast and colon cancers further supports its role as a therapeutic target.
Purpose of the Study:
- To synthesize and evaluate novel compounds targeting aurora kinases for their potential as antitumorigenic agents.
- To assess the in vitro and in vivo biological activity of three newly synthesized aurora kinase inhibitors: TC-28, TC-34, and TC-107.
- To identify a specific inhibitor of aurora A kinase that could offer a new therapeutic avenue for cancers with aurora A over-expression.
Main Methods:
- Synthesis of three novel aurora kinase inhibitors: TC-28, TC-34, and TC-107.
- In vitro assessment of the inhibitory properties of the synthesized compounds against aurora kinases.
- Evaluation of the biological activity and cellular effects of these inhibitors in human tissue culture cell lines.
Main Results:
- The synthesized compounds TC-28, TC-34, and TC-107 demonstrated aurora kinase inhibitory activity.
- TC-28 exhibited properties consistent with specific inhibition of aurora A kinase.
- The study confirmed the potential of TC-28 as a selective aurora A inhibitor in biological systems.
Conclusions:
- Novel aurora kinase inhibitors, including TC-28, have been successfully synthesized.
- TC-28 shows significant potential as a specific aurora A inhibitor for in vivo applications.
- These findings support the development of TC-28 as a targeted therapy for cancers over-expressing aurora A kinase, potentially overcoming resistance mechanisms.
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