Lost in Transcription: Finding Potential Small Molecule Inhibitors of Transcription Factor C-Myc

Mentor: Dina Wassaf

C-Myc is a transcription factor that regulates many genes, including those involved in cell proliferation. Over-expression of c-Myc is found in cancer cells, and therefore compounds inhibiting c-Myc when it is up-regulated could be used as cancer treatments.

Rachel sought to find a small molecule inhibitor of c-Myc. To this end, Rachel used Small Molecule Microarrays (SMM) to screen c-Myc against over 20,000 unique small molecules, in order to identify compounds that bind to c-Myc. Rachel’s screen produced a 1.3% hit rate, and she found compounds that gave the highest signal (implying strong binding to c-Myc) and the lowest variance (implying consistent binding to c-Myc). She discovered three large structural clusters containing several related members, all of which bind to c-Myc. Future testing for affinity of these compounds to c-Myc, inhibition of activity of c-Myc, and mechanism of inhibition will be performed. Compounds successfully undergoing these tests may one day be developed as anti-cancer drugs.

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Rachel, a senior at Concord Academy, utilized small molecule microarrays to discover chemical compounds that inhibit the transcription factor c-Myc.