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Design of granulatimide and isogranulatimide analogues as potential Chk1 inhibitors: Study of amino-platforms for their synthesis
Affiliation:1. School of Public Health, Medical College of Soochow University, Suzhou, China;2. Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, China;3. Microbeam Development Office, Research/Development/Support Center, National Institute of Radiological Sciences, Chiba, Japan;4. School of Radiological Medicine and Protection, Medical College of Soochow University, Suzhou, China;1. Department of Chemistry and Materials Science, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, Huelva 21007, Spain;2. Research Center on Health and Environment (CYSMA), University of Huelva, Spain;3. International Campus of Excellence on Agrofood (ceiA3), University of Huelva, Spain;4. Department of Environmental Biology and Public Health, Cell Biology, Faculty of Experimental Sciences, University of Huelva, Campus El Carmen, Huelva 21007, Spain;1. Department of Mechanical & Industrial Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA;2. Process Technologies Department, ExxonMobil Research & Engineering, Annandale, NJ 08801, USA;1. Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK;2. Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, UK;3. Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK;1. Department of Cancer Chemistry, Oncology IMED, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, United States;2. Chemistry Innovation Center, Discovery Sciences, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, United States;3. Department of Cancer Bioscience, Oncology IMED, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, United States;4. Acetylon Pharmaceuticals, Inc., Seaport Center, 70 Fargo Street, Suite 205, Boston, MA 02210, United States;5. Biogen Idec, 12 Cambridge Center, Cambridge, MA 02142, United States;6. Department of Infection Chemistry, Infection IMED, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, United States;7. Biortus Biosciences, Building A5, 6 Dongsheng West Road, Jiangyin, Jiangsu Province 214437, China;1. Medicinal Chemistry and Natural Products Research Group, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, Merseyside, UK;2. Manchester Interdisciplinary Biocentre, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK;3. The Department of Chemistry, University of Reading, Reading RG6 6AD, UK
Abstract:The two marine alkaloids granulatimide and isogranulatimide have been shown to inhibit the checkpoint kinase 1 (Chk1), a promising target for cancer treatment. A molecular docking study allowing the design of new potential Chk1 inhibitors based on the natural products skeleton and the synthetic work to an amino-target platform to prepare them are described.
Keywords:Marine alkaloid  Isogranulatimide  Granulatimide  Chk1 inhibitors
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