Integrative Research Centers
Chemical Biology Initiative
Gregory 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.