Proteasome Inhibitors

Since our initial discovery that the microbially-derived natural products epoxomicin and eponemycin represent a new class of proteasome inhibitors, we have focused on the development of additional inhibitors based on this epoxyketone proteasome-selective pharmacophore.  These studies have also led us to explore the chemistry and biology of other proteasome inhibitors such as the neurotrophic natural product fellutamide B and the natural product TMC-95A/B.

Relevant Publications

Hines J, Groll M, Fahnestock M, Crews CM
Chemistry & Biology 2008 15 5 501-512
Schneekloth JS Jr., Sanders JL, Hines J, Crews CM
Bioorg Med Chem Lett. 2006 16 14 3855-3858
Kim KB, Fonseca F, Crews CM
Methods Enzymol 2005 399 585-609
Garrett IR, Chen D, Gutierrez G, Zhao M, Excobedo A, Rossini G, Harris SE, Gallwitz W, Kim KB, Hu S, Crews CM, Munch GR
J. Clin Invest. 2003 111 11 1771-1782