Each year, many promising natural products are identified as being biologically active in cell culture assays.  Despite their proven in vitro efficacies, development of these 'drug candidates' into clinically useful therapeutic agents is an arduous procedure.  Initially discovered by Bristol-Myers Squibb, the microbial anti-tumor natural product epoxomicin was not initially developed as a drug candidate due to 1) its peptide structure, 2) potentially labile epoxyketone pharmacophore, and 3) lack of a known mode of action.  After developing the first total synthesis of epoxomicin, the Crews lab discovered it be a potent and selective proteasome inhibitor with a unique pharmacophore.  Further optimization by the Crews lab yielded the synthetic tetrapeptide epoxyketone YU-101, which served as the parent compound for Carfilzomib (Kyprolis�), the newly approved therapeutic agent for multiple myeloma.

Carfilzomib/Kyprolis<sup>TM</sup>: The next generation proteasome inhibitor inspired by Nature

247th National Meeting (2014)

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Carfilzomib/KyprolisTM: The next generation proteasome inhibitor inspired by Nature

Carfilzomib/Kyprolis^TM: The next generation proteasome inhibitor inspired by Nature