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Recent advances in the discovery and development of glyoxalase I inhibitors
Institution:1. Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, People’s Republic of China;2. Sichuan Institute for Food and Drug Control, Chengdu 611731, People’s Republic of China;3. Department of Chemistry, School of Science, Beijing Technology and Business University, Beijing 100048, People’s Republic of China;1. Pharmaceutical Department, 251 General Air Force Hospital, 11525 Athens, Greece;2. Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54214 Thessaloniki, Greece;3. Department of Pharmaceutical Chemistry, School of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, Greece;4. Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dubravska Cesta 9, 841 04 Bratislava, Slovakia;1. College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian 116044, PR China;2. Department of Hematology, Institute of Respiratory Diseases, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China;3. Dalian Buyun Biological Technology Co., Ltd., 116085, PR China;1. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Palatucci, 13, I-98168 Messina, Italy;2. Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria;3. Department of Microbiology and Immunology, Lab. of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium;1. La Trobe Institute for Molecular Science, La Trobe University, Victoria 3086, Australia;2. School of Science, University of New South Wales, Canberra 2610, Australia;3. School of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia;4. Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia;5. Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia;1. Division of Medicinal and Natural Products Chemistry, Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, 115 S Grand Ave., S321 Pharmacy Building, Iowa City, IA 52242, USA;2. Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA
Abstract: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.
Keywords:Natural or natural product-based inhibitors  GSH-based inhibitors  Non-GSH-based inhibitors  High throughput screening  Photo-affinity labeling and affinity pull-down protocols  Fragment-based drug discovery strategy
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