title: CDDO and Its Role in Chronic Diseases.
abstract: There has been a continued interest in translational research focused on both natural products and manipulation of functional groups on these compounds to create novel derivatives with higher desired activities. Oleanolic acid, a component of traditional Chinese medicine used in hepatitis therapy, was modified by chemical processes to form 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO). This modification increased anti-inflammatory activity significantly and additional functional groups on the CDDO backbone have shown promise in treating conditions ranging from kidney disease to obesity to diabetes. CDDO's therapeutic effect is due to its upregulation of the master antioxidant transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) through conformational change of Nrf2-repressing, Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) and multiple animal and human studies have verified subsequent activation of Nrf2-controlled antioxidant genes via upstream Antioxidant Response Element (ARE) regions. At the present time, positive results have been obtained in the laboratory and clinical trials with CDDO derivatives treating conditions such as lung injury, inflammation and chronic kidney disease. However, clinical trials for cancer and cardiovascular disease have not shown equally positive results and further exploration of CDDO and its derivatives is needed to put these shortcomings into context for the purpose of future therapeutic modalities.
authors: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina, 29208, USA.
authors: Bryan J
authors: BJ
authors: Mathis
authors: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, 6439 Garners Ferry Rd., Columbia, South Carolina, 29209, USA. Taixing.Cui@uscmed.sc.edu.
authors: Taixing
authors: T
authors: Cui
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000975:Antioxidants / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002908:Chronic Disease / Q000188:drug therapy*; D055808:Drug Discovery / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008516:Medicine, Chinese Traditional; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D008517:Phytotherapy; D010946:Plants, Medicinal; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: C116817:2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid; D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D002317:Cardiovascular Agents; D009828:Oleanolic Acid
keywords: Apoptosis; Bardoxolone; CDDO; CDDO-Im; CDDO-Me; Cardiorenal; Hepatotoxic; Keap1; Nrf2; TFEA; Vascular; dh404