黄嘌呤氧化还原酶抑制剂研究进展

Research progress of xanthine oxidoreductase in biological functions and its inhibitor development

黄嘌呤氧化还原酶为钼蛋白酶家族成员,最被人们所知的生物学功能是催化嘌呤分解代谢,生成尿酸并伴随大量活性氧产生,与痛风发生密切相关。近年研究发现其还参与其他物质代谢,同时与缺血/再灌注损伤、心血管疾病尤其与心衰密切相关,而其抑制剂对这些疾病具有较好的治疗作用,因而针对此靶点的药物研发又受到广泛关注。

xanthine oxidoreductase （XOR）is a member of the molybcloenzyme family and best known for its catalytic role in purine degradation, metabolizing hypoxanthine and xanthine to uric acid with concomitant generation of superoxide and hydrogen peroxide. In addition to its role in the pathophysiology of hyperuricaemia and gout, the role for XOR beyond purine metabolism was first suggested in ischaemia-reperfusion injury, there is growing evidence that it also participates in endothelial dysfunction, hypertension and heart failure. Importantly, the XOR inhibitor attenuates dvsfunction especially in heart failure caused by XOR in these disease states. Attention to the broader range of XOR bioactivity in the cardiovascular system has prompted strong interest based XOR drug development by pharmaceuticals company.