Our laboratory also has a keen interest in collaborating with biological investigators to identify bioactive molecules. For example, we have synthesized more than 100 analogs of the rocaglates, known to be potent translation inhibitors with activity in several cancers from our collaboration with Dr. Jerry Pelletier at McGill University. Our collaboration with the BU-CMD has since enabled evaluation of these compounds in additional therapeutic areas with several impactful results. Dr. Luke Whitesell (Whitehead Institute) identified rocaglamide A (RocA) as a potent and selective inhibitor of heat-shock induced reporter gene expression. They later identified CMLD010515 for use in treating acute myeloid leukemia. Similar rocaglates such as CMLD010509 were identified by the Pelletier lab and in later studies with Dr. Irene Ghobrial at DFCI/HMS who studied the compound effects in mouse models of multiple myeloma. Dr. Igor Kramnik (BU NEIDL) identified CMLD010509 as a potent inducers of Irf-1 induction, stimulating host immune response to tuberculosis. Our collaborator Dr. Tony Wang at SRI has identified additional rocaglate family members such as CMLD10833 that prevent viral entry in hepatitis C virus (HCV).
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