title: [Classification and synthesis of ubiquitin-proteasome inhibitor].
abstract: The inhibition of protein degradation through the ubiquitin-proteasome pathway is a recently developed approach to cancer treatment which extends the range of cellular target for chemotherapy. This therapeutic strategy is very interesting since the proteasomes carry out the regulated degradation of unnecessary or damaged cellular proteins, a process that is dysregulated in many cancer cells. Based on this hypothesis, the proteasome complex inhibitor Bortezomib was approved for use in multiple myeloma patients by FDA in 2003. Drug discovery programs in academy and the pharmaceutical industry have developed a range of synthetic and natural inhibitors of the 20S proteasome core particle that have entered human clinical trials as significant anti-cancer leads. The main results from the use of proteasome inhibition in cancer chemotherapy, the structure of several proteasome inhibitors and their synthesis is going to be reviewed in this paper.
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Zhang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wu
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000145:classification / Q000627:therapeutic use; D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D000069286:Bortezomib; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000145:classification*; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy / Q000201:enzymology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D025801:Ubiquitin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D010456:Peptides, Cyclic; D061988:Proteasome Inhibitors; D011719:Pyrazines; C408291:TMC-95A; D025801:Ubiquitin; C449021:tyropeptin A; C067713:lactacystin; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine