期刊
MEDICINAL CHEMISTRY RESEARCH
卷 26, 期 12, 页码 3274-3285出版社
SPRINGER BIRKHAUSER
DOI: 10.1007/s00044-017-2020-9
关键词
Virtual screening; Docking; Casein Kinase 1; Alzheimer's disease; Neurodegenerative disease
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP [2010/14929-3]
Alzheimer's disease is a progressive neurodegenerative disorder characterized by loss of neurons. Pathological patterns include the presence of amyloid plaques (accumulation of amyloid-beta protein fragments) and neurofibrillary tangles. Only two major groups of drugs are used in Alzheimer's disease's treatment: cholinesterase inhibitors and antagonists of N-methyl-D-aspartate receptor. The phosphorylation of proteins by protein kinases constitutes one of the major mechanism by which cells use to regulate their metabolism. Imbalance in these activities is related to a series of diseases. The high number of casein kinase 1 isoforms found in Alzheimer's disease brains and its association with neurodegenerative markers indicates their participation in the final stages of Alzheimer's disease degeneration. In this study, it was employed structure-based virtual screening techniques in a chemical space of 500 thousand chemical structures. The ten chemical structures with the best inhibitory profile for casein kinase 1 were then selected for activity and toxicity predictions. The compounds 11 (ZINC48488295), 14 (ZINC04869366) and 17 (ZINC4412706) presented significant potential for CK1 delta enzyme inhibition.
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