Specific small-molecule activator of aurora kinase a induces autophosphorylation in a cell-free system

Hari Kishore, A. and Vedamurthy, B. M. and Mantelingu, K. and Shipra Agrawal and Ashok Reddy, B. A. and Roy, Siddhartha and Rangappa, K. S. and Kundu, Tapas K. (2008) Specific small-molecule activator of aurora kinase a induces autophosphorylation in a cell-free system. Journal of Medicinal Chemistry, 51 (4). pp. 792-797. ISSN 1520-4804

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Official URL: https://doi.org/10.1021/jm700954w

Abstract

Aurora kinases are essential for chromosomal segregation and cell division and thereby important for maintaining the proper genomic integrity. There are three classes of aurora kinases in humans: A, B, and C. Aurora kinase A is frequently overexpressed in various cancers. The link of the overexpression and tumorigenesis is yet to be understood. By employing virtual screening, we have found that anacardic acid, a pentadecane aliphatic chain containing hydroxylcarboxylic acid, from cashew nut shell liquid could be docked in Aurora kinases A and B. Remarkably, we found that anacardic acid could potently activate the Aurora kinase A mediated phosphorylation of histone H3, but at a similar concentration the activity of aurora kinase B remained unaffected in vitro. Mechanistically, anacardic acid induces the structural changes and also the autophosphorylation of the aurora kinase A to enhance the enzyme activity. This data thus indicate anacardic acid as the first small-molecule activator of Aurora kinase, which could be highly useful for probing the function of hyperactive (overexpressed) Aurora kinase A.

Item Type: Article
Additional Information: PMID: 18215015
Subjects: C Chemical Science > Chemistry
Divisions: Department of > Chemistry
Depositing User: manjula User
Date Deposited: 26 Aug 2019 07:37
Last Modified: 26 Aug 2019 07:37
URI: http://eprints.uni-mysore.ac.in/id/eprint/7036

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