Computational discovery and biological evaluation of novel inhibitors targeting histone-lysine N-methyltransferase SET7 |
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| Institution: | 1. State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China;2. Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China;3. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China;4. University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China;1. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII avenue, Cardiff CF10 3NB, UK;2. Green Chemistry Department, National Research Centre, Cairo, Egypt;3. Department of Pharmaceutical Chemistry, Cairo University, Cairo, Egypt;1. Department of Orthopedics, Heilongjiang Province Hospital, Harbin 150036, Heilongjiang Province, China;2. Department of Orthopedics, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China;3. Department of Orthopedics, Traditional Chinese Medicine Hospital of Harbin, Harbin 150000, Heilongjiang Province, China;4. Department of Orthopedics, Affiliated Hospital of Putian University, Putian 351100, Fujian Province, China;1. Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, United States;2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, United States;1. Institute of Cytology, Russian Academy of Sciences, 194064, St Petersburg, Russian Federation;2. Almazov National Medical Research Centre, Institute of Hematology, 197341, St Petersburg, Russian Federation;3. N.N. Petrov Institute of Oncology, 197758, Saint-Petersburg, Russian Federation;4. Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Moscow Region, Russian Federation;1. Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA;2. Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA;3. Yerkes National Primate Research Center, Emory University, 201 Dowman Drive, Atlanta, GA 30322, USA;1. Department of Chemistry, University of South Florida, CHE 205, 4202 E. Fowler Avenue, Tampa, FL 33620, USA;2. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, 4202 E Fowler Ave, Tampa, FL, USA |
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| Abstract: | Histone-lysine N-methyltransferase SET7 emerged as a potential target for multiple cancers. In a virtual screening program used to explore new and potent inhibitors of SET7, compound 16 was discovered as a top hit with an IC50 value of 6.02 μM. A further similarity search afforded a new compound 23, which exhibited better activity against SET7 with an IC50 value of 1.96 μM. Importantly, compound 23 selectively inhibited the proliferation of MV4-11 cells. Comprehensively, compound 23 can serve as a lead for further identification and development of more potent SET7 inhibitors. |
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| Keywords: | Histone methylation Lysine methyltransferase SET7 Small-molecule inhibitor Virtual screening |
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