Open Access
Frontiers in Chemistry, volume 9
Scaffold Searching of FDA and EMA-Approved Drugs Identifies Lead Candidates for Drug Repurposing in Alzheimer’s Disease
2
Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, W�rzburg University Hospital, Germany
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3
Department of Bioinformatics, Biocenter, University of W�rzburg, Germany
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Publication type: Journal Article
Publication date: 2021-10-22
Journal:
Frontiers in Chemistry
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor: 5.5
ISSN: 22962646
PubMed ID:
34751244
General Chemistry
Abstract
Clinical trials of novel therapeutics for Alzheimer’s Disease (AD) have consumed a significant amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA), European Medicines Agency (EMA), or Worldwide for another indication is a more rapid and less expensive option. Therefore, we apply the scaffold searching approach based on known amyloid-beta (Aβ) inhibitor tramiprosate to screen the DrugCentral database (n = 4,642) of clinically tested drugs. As a result, menadione bisulfite and camphotamide substances with protrombogenic and neurostimulation/cardioprotection effects were identified as promising Aβ inhibitors with an improved binding affinity (ΔGbind) and blood-brain barrier permeation (logBB). Finally, the data was also confirmed by molecular dynamics simulations using implicit solvation, in particular as Molecular Mechanics Generalized Born Surface Area (MM-GBSA) model. Overall, the proposed in silico pipeline can be implemented through the early stage rational drug design to nominate some lead candidates for AD, which will be further validated in vitro and in vivo, and, finally, in a clinical trial.
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Citations by publishers
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1
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4
5
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Multidisciplinary Digital Publishing Institute (MDPI)
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5 publications, 45.45%
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Wiley
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1 publication, 9.09%
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1 publication, 9.09%
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Taylor & Francis
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Taylor & Francis
1 publication, 9.09%
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Springer Nature
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Springer Nature
1 publication, 9.09%
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American Chemical Society (ACS)
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American Chemical Society (ACS)
1 publication, 9.09%
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Future Medicine
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Future Medicine
1 publication, 9.09%
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Shityakov S. et al. Scaffold Searching of FDA and EMA-Approved Drugs Identifies Lead Candidates for Drug Repurposing in Alzheimer’s Disease // Frontiers in Chemistry. 2021. Vol. 9.
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Shityakov S., Skorb E. V., Förster C. Y., DANDEKAR T. Scaffold Searching of FDA and EMA-Approved Drugs Identifies Lead Candidates for Drug Repurposing in Alzheimer’s Disease // Frontiers in Chemistry. 2021. Vol. 9.
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TY - JOUR
DO - 10.3389/fchem.2021.736509
UR - https://doi.org/10.3389%2Ffchem.2021.736509
TI - Scaffold Searching of FDA and EMA-Approved Drugs Identifies Lead Candidates for Drug Repurposing in Alzheimer’s Disease
T2 - Frontiers in Chemistry
AU - Shityakov, Sergey
AU - Skorb, Ekaterina V
AU - Förster, Carola Y.
AU - DANDEKAR, THOMAS
PY - 2021
DA - 2021/10/22 00:00:00
PB - Frontiers Media S.A.
VL - 9
PMID - 34751244
SN - 2296-2646
ER -
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@article{2021_Shityakov,
author = {Sergey Shityakov and Ekaterina V Skorb and Carola Y. Förster and THOMAS DANDEKAR},
title = {Scaffold Searching of FDA and EMA-Approved Drugs Identifies Lead Candidates for Drug Repurposing in Alzheimer’s Disease},
journal = {Frontiers in Chemistry},
year = {2021},
volume = {9},
publisher = {Frontiers Media S.A.},
month = {oct},
url = {https://doi.org/10.3389%2Ffchem.2021.736509},
doi = {10.3389/fchem.2021.736509}
}
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