期刊
EXPERT OPINION ON DRUG DISCOVERY
卷 14, 期 11, 页码 1175-1197出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17460441.2019.1651289
关键词
Carbonic anhydrase; inhibitor; activator; sulfonamide; coumarin; SLC-0111; inhibition mechanism; X-ray crystallography
Introduction: Of the 15 human carbonic anhydrase (CA, EC 4.2.1.1) isoforms known to date, for 11 the crystal structure is known. Many different classes of CA inhibitors (CAIs) were reported in the last decade, with a wealth of inhibition mechanisms, where apart from the classical one, the inhibitors do not bind to the zinc ion from the active site. The zinc binders (sulfonamides, dithiocarbamates and their isosteres, thiols, selenols, carboxylates, hydroxamates, carbamates) are not isoform-selective inhibitors, but the specificity of action may be achieved by decorating their scaffolds with tails that interact with amino acids at the entrance of the active site. Areas covered: Herein, the authors review the advances in the structural annotation of human CAs. Furthermore, the authors look at the impact on drug discovery efforts as well as providing their expert perspectives. Expert opinion: CAs are a unique example among metalloenzymes for which all regions of their spacious active sites may be used for inhibitor/activator binding, leading to a variety of inhibition mechanisms and profiles for the many chemotypes modulating their activity. This is exploited for the drug design of increasingly efficient and isoform-selective inhibitors, useful for many pharmacological applications.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据