title: Synthesis and pharmacology of proteasome inhibitors.
abstract: Shortly after the discovery of the proteasome it was proposed that inhibitors could stabilize proteins which ultimately would trigger apoptosis in tumor cells. The essential questions were whether small molecules would be able to inhibit the proteasome without generating prohibitive side effects and how one would derive these compounds. Fortunately, "Mother Nature" has generated a wide variety of natural products that provide distinct selectivities and specificities. The chemical synthesis of these natural products finally provided access to analogues and optimized drugs of which two different classes have been approved for the treatment of malignancies. Despite these achievements, additional lead structures derived from nature are under investigation and will be discussed with regard to their biological potential and chemical challenges.
authors.affiliation: Institut für Organische Chemie and Centre of Biomolecular Drug Research, Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rentsch
authors.forename: Dirk
authors.initials: D
authors.lastname: Landsberg
authors.forename: Tobias
authors.initials: T
authors.lastname: Brodmann
authors.forename: Leila
authors.initials: L
authors.lastname: Bülow
authors.forename: Anna-Katharina
authors.initials: AK
authors.lastname: Girbig
authors.forename: Markus
authors.initials: M
authors.lastname: Kalesse
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease