Discovery and Structure-Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening (5JYW withdrawn)
Revelation date
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27-Jul-2016
Family
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BCHE: there are 91 genes in this family, 92 structure(s)
Structure-based virtual screening of two libraries containing 567981 molecules was used to discover novel, selective BuChE inhibitors, which are potentially superior symptomatic treatments in late-stage Alzheimer's disease. Compound 16 was identified as a highly selective submicromolar inhibitor of BuChE (huBuChE IC50 = 0.443 muM) with high permeability in the PAMPA-BBB model. The X-ray crystal structure of huBuChE in complex with 16 revealed the atomic-level interactions and offers opportunities for further development of the series.
Representative scheme of BCHE structure and an image from PDBsum server
Databases
PDB-Sum
5K5E Previously Class, Architecture, Topology and Homologous superfamily - PDB-Sum server
FSSP
5K5EFold classification based on Structure-Structure alignment of Proteins - FSSP server
