Non-peptidic natural products as ubiquitin-proteasome inhibitors

摘要: Abstract Approval of bortezomib has validated ubiquitin-proteasome pathway as an important target for treatment haematological malignancies. However, clinical shortcomings bortezomib, a covalent peptide proteasome inhibitor, prompted paradigm shift in anti-proteasome drug discovery towards development non-peptidic inhibitors and targeting upstream ubiquitin system which drawn traction interdisciplinary forays. It is being widely recognized that natural products provide valuable leads the potent, chemically diverse, 20S key enzymes involved ubiquitination machinery. As result, total synthesis natural, emerged critical interlink between organic synthesis, medicinal chemistry, biochemical profiling discovery. An up-to-date account contextual synthetic challenges, strategies accomplishments well mapping chemical diversity space around scaffolds been captured this review.