title: Hyperuricemia-Related Diseases and Xanthine Oxidoreductase (XOR) Inhibitors: An Overview.
abstract: Uric acid is the final oxidation product of purine metabolism in humans. Xanthine oxidoreductase (XOR) catalyzes oxidative hydroxylation of hypoxanthine to xanthine to uric acid, accompanying the production of reactive oxygen species (ROS). Uric acid usually forms ions and salts known as urates and acid urates in serum. Clinically, overproduction or under-excretion of uric acid results in the elevated level of serum uric acid (SUA), termed hyperuricemia, which has long been established as the major etiologic factor in gout. Accordingly, urate-lowering drugs such as allopurinol, an XOR-inhibitor, are extensively used for the treatment of gout. In recent years, the prevalence of hyperuricemia has significantly increased and more clinical investigations have confirmed that hyperuricemia is an independent risk factor for cardiovascular disease, hypertension, diabetes, and many other diseases. Urate-lowering therapy may also play a critical role in the management of these diseases. However, current XOR-inhibitor drugs such as allopurinol and febuxostat may have significant adverse effects. Therefore, there has been great effort to develop new XOR-inhibitor drugs with less or no toxicity for the long-term treatment or prevention of these hyperuricemia-related diseases. In this review, we discuss the mechanism of uric acid homeostasis and alterations, updated prevalence, therapeutic outcomes, and molecular pathophysiology of hyperuricemia-related diseases. We also summarize current discoveries in the development of new XOR inhibitors.
authors.affiliation: Division of Surgical Research, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Changyi
authors.initials: C
authors.lastname: Chen
authors.affiliation: Division of Surgical Research, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Lü
authors.affiliation: Division of Surgical Research, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yao
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000069465:Febuxostat / Q000494:pharmacology; D006801:Humans; D033461:Hyperuricemia / Q000201:enzymology* / Q000628:therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D000069465:Febuxostat; D000493:Allopurinol; D014968:Xanthine Dehydrogenase