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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Discovery of potential neurodegenerative inhibitors in Alzheimer's disease by casein kinase 1 structure-based virtual screening

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Rodrigues, Ricardo P. [1, 2] ; da Silva, Carlos H. T. P. [1]
Total Authors: 2
[1] Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo - Brazil
[2] Univ Fed Espirito Santo, Dept Pharmaceut Sci, Vitoria, ES - Brazil
Total Affiliations: 2
Document type: Journal article
Source: MEDICINAL CHEMISTRY RESEARCH; v. 26, n. 12, p. 3274-3285, DEC 2017.
Web of Science Citations: 4

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. (AU)

FAPESP's process: 10/14929-3 - Casein kinase 1 as a target for drug design in Alzheimer's Disease
Grantee:Ricardo Pereira Rodrigues
Support type: Scholarships in Brazil - Doctorate