Physicochemistry shapes bioactivity landscape of pan-ABC transporter modulators: Anchor point for innovative Alzheimer's disease therapeutics
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F22%3A10458085" target="_blank" >RIV/00179906:_____/22:10458085 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=i5UldptW7V" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=i5UldptW7V</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ijbiomac.2022.07.062" target="_blank" >10.1016/j.ijbiomac.2022.07.062</a>
Alternative languages
Result language
angličtina
Original language name
Physicochemistry shapes bioactivity landscape of pan-ABC transporter modulators: Anchor point for innovative Alzheimer's disease therapeutics
Original language description
Alzheimer's disease (AD) is a devastating neurological disorder characterized by the pathological accumulation of macromolecular A beta and tau leading to neuronal death. Drugs approved to treat AD may ameliorate disease symptoms, however, no curative treatment exists. A beta peptides were discovered to be substrates of adenosine triphosphate-(ATP)-binding cassette (ABC) transporters. Activators of these membrane-bound efflux proteins that promote binding and/or translocation of A beta could revolutionize AD medicine. The knowledge about ABC transporter activators is very scarce, however, the few molecules that were reported contain substructural features of multitarget (pan-)ABC transporter inhibitors. A cutting-edge strategy to obtain new drug candidates is to explore and potentially exploit the recently proposed multitarget binding site of pan-ABC transporter inhibitors as anchor point for the development of innovative activators to promote A beta clearance from the brain. Molecular associations between functional bioactivities and physicochemical properties of small-molecules are key to understand these processes. This study provides an analysis of a recently reported unique multitarget dataset for the correlation between multitarget bioactivity and physicochemistry. Six novel pan-ABC transporter inhibitors were validated containing substructural features of ABC transporter activators, which underpins the relevance of the multitarget binding site for the targeted development of novel AD diagnostics and therapeutics.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
International Journal of Biological Macromolecules
ISSN
0141-8130
e-ISSN
1879-0003
Volume of the periodical
217
Issue of the periodical within the volume
September
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
17
Pages from-to
775-791
UT code for WoS article
000919287800005
EID of the result in the Scopus database
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