Identifying Effective Small Molecule Inhibitors of Aurora A Kinase

Mentors: Katie Doud and Angela Koehler

Aurora A kinase, a protein commonly found to be over-expressed in many types of cancer cells, is believed to play an important role in cancer development.  Michael and his mentors aimed to identify effective small-molecule inhibitors of Aurora A that might someday be developed into anti-cancer drugs.  

To this end, Michael studied 15 chemicals found previously to bind to Aurora A. Michael measured the concentration of each inhibitor at which 50% of the Aurora A is inhibited (the “IC50 value”).  The compound TLII-211 inhibited Aurora A most effectively. Michael then found that the IC50 values for TLII-211 did not change in the presence of ATP, suggesting that this inhibitor is not competitive with ATP and can therefore be further considered as a potential drug.  Finally, Michael determined that TLII-211 showed synergistic behavior with VX680, a compound already in clinical trials.  Based on Michael’s findings, TLII-211 will be investigated further for its use as an Aurora A kinase inhibitor.

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Michael, a senior at Malden High School, identified and characterized small molecules that inhibit Aurora A kinase.


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