Aurora libraries. Aurora A-B Kinases Targeted Library

Aurora Kinase Inhibitors Library

ChemDiv’s library of inhibitors of aurora kinases comprises a set of 10,000 compounds.

Aurora kinases are a family of serine/threonine kinases that includes Aurora A (AURKA), Aurora B (AURKB), and Aurora C (AURKC). They are critical components for cell division pathways, especially for controlling mitosis and chromosome segregation. In addition to their role in mitosis, these kinases are also involved in the regulation of meiosis. The down-regulation of Aurora kinase activity can lead to the failure of cell division and impair embryonic development. Overexpression or gene amplification of Aurora kinases has been identified in numerous cancers, and an increasing body of research has demonstrated that inhibiting these kinases can enhance the efficacy of chemotherapy treatments. Over the past few decades, a series of Aurora kinase inhibitors (AKIs) have been developed, effectively suppressing the progression and growth of various cancers both in vivo and in vitro. This underscores the potential of Aurora kinases as novel therapeutic targets in oncology drug discovery [1].

Therefore, AKIs play a crucial role in drug discovery, particularly in the field of oncology, due to their ability to target key regulators of cell division and mitosis. By inhibiting aurora kinases, which are often overexpressed or amplified in various cancers, these inhibitors can disrupt abnormal cell proliferation and growth, a hallmark of cancer. The development of AKIs is aimed at inducing apoptosis in cancer cells and halting tumor progression. Their utility has been demonstrated in a range of cancers, showing promise in both in vitro and in vivo studies. As such, AKIs are considered potential candidates for targeted cancer therapies, offering a more precise approach compared to traditional chemotherapeutic agents.

Currently, the Protein Data Bank (PDB) houses over 100 crystallographic complexes of various small-molecule AKIs. A 3D model of the aurora kinase active site was reconstructed using selected X-ray data (PDB IDs: 4JAI and 2BFY). Reference compounds and molecules from our library were then docked into this constructed model, starting from 2D structures without predefined stereochemistry. The docking results showed good correlation with the reference SAR data used, with an average RMSD of 0.3. Representative compounds from ChemDiv's library have demonstrated a binding mode similar to that of reported aurora kinase inhibitors, indicating their potential efficacy in targeting known types of aurora kinases.

References

[1] A. Tang, K. Gao, L. Chu, R. Zhang, J. Yang, and J. Zheng, “Aurora kinases: Novel therapy targets in cancers,” Oncotarget, vol. 8, no. 14, pp. 23937–23954, 2017, doi: 10.18632/oncotarget.14893.