高尿酸血症
非布索坦
黄嘌呤氧化酶
黄嘌呤氧化酶抑制剂
别嘌呤醇
痛风
尿酸
嘌呤
药理学
嘌呤代谢
化学
次黄嘌呤
药物发现
黄嘌呤
药品
生物化学
医学
酶
内科学
作者
Giuseppe Antonio Di Luna,Anton V. Dolzhenko,Ricardo L. Mancera
出处
期刊:ChemMedChem
[Wiley]
日期:2019-03-05
卷期号:14 (7): 714-743
被引量:60
标识
DOI:10.1002/cmdc.201900034
摘要
Xanthine oxidase (XO) is the enzyme responsible for the catabolism of purines and their conversion into uric acid. XO is thus the target for the treatment of hyperuricemia and gout. For more than 50 years the only XO inhibitor drug available on the market was the purine analogue allopurinol. In the last decade there has been a resurgence in the search for new inhibitors of XO, as the activity of XO and hyperuricemia have also been associated with a variety of conditions such as diabetes, hypertension, and other cardiovascular diseases. In recent years the non-purine inhibitor febuxostat was approved in Europe and the USA for the treatment of hyperuricemia. This drug was followed by another XO inhibitor called topiroxostat. This review discusses the molecular structures and activities of the multiple classes of inhibitors that have been developed since the discovery of allopurinol, with a brief review of the molecular interactions between inhibitors and XO active site residues for the most important molecules. The challenges ahead for the discovery of new inhibitors of XO with novel chemical structures are discussed.
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