• Integrative Research Centers

    Chemical Biology Initiative

    Director: Gregory Verdine, PhD

    gregory-verdine.jpgGregory Verdine, PhD 

    The Chemical Biology Initiative provides molecular solutions to problems posed by cancer, fostering basic biological discoveries and the translation of these discoveries into new drugs for cancer patients. Five core groups have scientific programs that focus on: the discovery of novel protein kinase inhibitors; molecules that enable dissection of chromosome management during cell division; mitochondrial events responsible for the initiation of programmed cell death; novel inhibitors of epigenetic chromatin modification and transcriptional activation; and development of new molecular platforms to target intractable targets in cancer. Members have numerous collaborations with investigators from other Dana-Farber integrative centers, Harvard-affiliated hospitals, and the Broad Institute. Recent accomplishments include:

    • Discovery of inhibitors that target Abl kinase through a novel mechanism and inhibitors that target both major arms of the Tor pathway
    • Discovery of small molecules that inhibit the Rho pathway
    • Discovery of a new class of drugs, "stapled" peptides, and their use in targeting intracellular protein-protein interactions that drive cancer
    • Discovery of a new mechanism for the induction of programmed cell death
    • Discovery of a role for the protein BAD in glucose sensing and the role of molecules that rescue BAD function
    • Discovery of the first potent cell-permeable inhibitors of an oncogenic transcription factor that was previously thought to be un-druggable
    • Discovery of potent and selective inhibitors of histone deacetylase 6.

    Several molecules created by the Initiative have demonstrated efficacy in mouse models of cancer. They are undergoing extensive optimization and preclinical safety and efficacy testing in preparation for clinical evaluation in the near future.

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