title: New synthetic triterpenoids: potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress.
abstract: We review the original rationale for the development and the chemistry of a series of new synthetic oleanane triterpenoids (SO), based on oleanolic acid (1) as a starting material. Many of the new compounds that have been made, such as 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid ("CDDO", 8), are highly potent (activities found at levels below 1 nM) anti-inflammatory agents, as measured by their ability to block the cellular synthesis of the enzyme inducible nitric oxide synthase (iNOS) in activated macrophages. Details of the organic synthesis of new SO and their chemical mechanisms of biological activity are reviewed, as is formation of biotin conjugates for investigation of protein targets. Finally, we give a brief summary of important biological activities of SO in many organ systems in numerous animal models. Clinical investigation of a new SO (methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate, "CDDO-Me", bardoxolone methyl, 13) is currently in progress.
authors.affiliation: Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, United States. Michael.Sporn@Dartmouth.edu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sporn
authors.forename: Karen T
authors.initials: KT
authors.lastname: Liby
authors.forename: Mark M
authors.initials: MM
authors.lastname: Yore
authors.forename: Liangfeng
authors.initials: L
authors.lastname: Fu
authors.forename: Justin M
authors.initials: JM
authors.lastname: Lopchuk
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Gribble
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D023421:Models, Animal; D015394:Molecular Structure; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D009828:Oleanolic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D017695:Soft Tissue Injuries / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D009828:Oleanolic Acid; D052247:Nitric Oxide Synthase Type II