Non-ATP competitive Inhibitors of Aurora Kinases: Selective and Potent Cancer Treatment
Summary Markets / Needs Addressed:Aurora kinases are overexpressed in many tumors including breast, cervical, colon, and pancreatic cancers. Aurora kinases are expressed only in actively dividing cells (e.g. tumor cells), hence they are more specific drug targets than microtubules. As many kinases are druggable, aurora kinases have become popular targets for cancer drug development. Examples of aurora kinase inhibitors under development include: VX-680 (Vertex and Merck), ZN447439 (AstraZeneca), and MLN8054 (Millennium). However, most aurora kinase inhibitors under clinical trials are ATP-competitive inhibitors that do not offer selectivity against other kinases. This lack of target specificity can result in adverse side effects in trial patients. Besides the advantage of kinase selectivity, non-ATP competitive inhibitors can perform better in the presence of ATP, i.e. in cells. For these reasons, non-ATP competitive kinase inhibitors are in demand in the pharmaceutical industry.
Applications Innovation and Advantages:
Using Diversity Oriented Synthesis (DOS), scientists at the Broad Institute have generated a new class of spirooxindole compounds inspired by natural product synthesis. These compounds inhibit aurora kinases in a non-ATP competitive manner, which results in higher selectivity than the existing ATP competitive inhibitors. These spirooxindole compounds have atypical structures for kinase inhibitors and therefore may provide new mechanism of actions for cancer treatments. Cell-based assays have shown that a lead spirooxindole compound decreases the viability of colorectal, colon, and breast cancer cell lines, with efficacy comparable to that of VX-680.
Patent Status: pending For Further Information Please Contact the Director of Business Development Laura Brass Email: [email protected] Telephone: (617) 495-3067
Inventor(s): Schreiber, Stuart L.
Type of Offer: Licensing
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