Recent advances in the discovery and development of glyoxalase I inhibitors

• Published in: Bioorganic & medicinal chemistry 2020-02, Vol.28 (4), p.115243-115243, Article 115243
• Main Authors: Jin, Tian, Zhao, Lu, Wang, Hong-Ping, Huang, Mao-Lin, Yue, Yan, Lu, Chichong, Zheng, Zhe-Bin
• Format: Article
• Language: English
• Subjects: Biological Products - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; Drug Development; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Fragment-based drug discovery strategy; GSH-based inhibitors; High throughput screening; Humans; Lactoylglutathione Lyase - antagonists & inhibitors; Lactoylglutathione Lyase - metabolism; Molecular Structure; Natural or natural product-based inhibitors; Non-GSH-based inhibitors; Photo-affinity labeling and affinity pull-down protocols
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2019.115243

[Display omitted] Glyoxalase I (GLO1) is a homodimeric Zn2+-metalloenzyme that catalyses the transformation of methylglyoxal (MG) to d-lacate through the intermediate S-d-lactoylglutathione. Growing evidence indicates that GLO1 has been identified as a potential target for the treatment cancer and other diseases. Various inhibitors of GLO1 have been discovered or developed over the past several decades including natural or natural product-based inhibitors, GSH-based inhibitors, non-GSH-based inhibitors, etc. The aim of this review is to summarize recent achievements of concerning discovery, design strategies, as well as pharmacological aspects of GLO1 inhibitors with the target of promoting their development toward clinical application.