Structure activity relationship, 6-modified purine riboside analogues to activate hSTING,stimulator of interferon genes |
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| Affiliation: | 1. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom;2. Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom;3. Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, 30 Flemington Road, Parkville, Victoria 3052, Australia;1. Department of Chemistry, College of Science, King Saud University, P.O Box 2455, Riyadh 11451, Saudi Arabia;2. Department of Botany, Davangere University, Shivagangothri, Davangere 577007, Karnataka, India;3. Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, A.P. 515 134, India;1. School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, Yunnan, China;2. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China;3. Department of Respiratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming 650031, Yunnan, China;1. New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, South Korea;2. Department of Biological Sciences, Ulsan National Institutes of Science and Technology (UNIST), Ulsan 44919, South Korea;3. College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, South Korea;4. Western Seoul Center, Korea Basic Science Institute, Seoul 03760, South Korea |
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| Abstract: | Twenty-nine nucleoside analogues have been synthesized and evaluated in a cell based assay for their ability to activate the human Stimulator of Interferon Genes (hSTING), a key protein of the innate immune defense. Some 6-O-alkyl nucleoside analogues activate hSTING without associated cytotoxicity. SAR and combination studies were performed to decipher possible activation mechanism. The described nucleoside hSTING activators represent first-in-class modulators of the innate immune defense; a highly relevant target for antiviral, antibacterial, anticancer or Alzheimer’s disease treatments and may present advantages over other types of hSTING activators. |
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| Keywords: | Innate immune response Interferons Nucleoside analogues Cell based assay |
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