肌苷单磷酸脱氢酶（IMPDH）作为药物研发的靶点。

Inosine monophosphate dehydrogenase (IMPDH) as a target in drug discovery.

作者信息

Shu Qingning, Nair Vasu

机构信息

The Center for Drug Discovery and the Department of Pharmaceutical and Biomedical Sciences, R. C. Wilson PH, University of Georgia, Athens, Georgia 30602, USA.

出版信息

Med Res Rev. 2008 Mar;28(2):219-32. doi: 10.1002/med.20104.

DOI:10.1002/med.20104

PMID:17480004

Abstract

Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme of de novo purine nucleotide biosynthesis and is viewed as an important target in the quest for discovery of drugs in the antiviral, antibacterial and anticancer therapeutic areas. This review focuses on the medicinal chemistry, drug discovery and chemical biology of IMPDH. Examples of IMP and cofactor site-directed inhibitors, allosteric inhibitors and isoform-selective inhibitors are presented. Comparison of IMPDHs from different organisms is also made to facilitate the design of species-selective IMPDH inhibitors for drug discovery. Special emphasis in the review is placed on IMPDH from Mycobacterium tuberculosis.

摘要

肌苷单磷酸脱氢酶（IMPDH）是嘌呤核苷酸从头生物合成的关键酶，被视为抗病毒、抗菌和抗癌治疗领域药物研发的重要靶点。本综述聚焦于IMPDH的药物化学、药物研发及化学生物学。文中介绍了肌苷单磷酸（IMP）和辅因子位点定向抑制剂、变构抑制剂及同工型选择性抑制剂的实例。还对不同生物体的IMPDH进行了比较，以促进用于药物研发的物种选择性IMPDH抑制剂的设计。本综述特别强调了结核分枝杆菌的IMPDH。