Investigation of New Orexin 2 Receptor Modulators Using In Silico and In Vitro Methods

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014983" target="_blank" >RIV/62690094:18470/18:50014983 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/18:10385034 RIV/60162694:G44__/18:43889676

Result on the web

<a href="http://dx.doi.org/10.3390/molecules23112926" target="_blank" >http://dx.doi.org/10.3390/molecules23112926</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules23112926" target="_blank" >10.3390/molecules23112926</a>

Result language

angličtina

Original language name

Investigation of New Orexin 2 Receptor Modulators Using In Silico and In Vitro Methods

Original language description

The neuropeptides, orexin A and orexin B (also known as hypocretins), are produced in hypothalamic neurons and belong to ligands for orphan G protein-coupled receptors. Generally, the primary role of orexins is to act as excitatory neurotransmitters and regulate the sleep process. Lack of orexins may lead to sleep disorder narcolepsy in mice, dogs, and humans. Narcolepsy is a neurological disorder of alertness characterized by a decrease of ability to manage sleep-wake cycles, excessive daytime sleepiness, and other symptoms, such as cataplexy, vivid hallucinations, and paralysis. Thus, the discovery of orexin receptors, modulators, and their causal implication in narcolepsy is the most important advance in sleep-research. The presented work is focused on the evaluation of compounds L1-L11 selected by structure-based virtual screening for their ability to modulate orexin receptor type 2 (OX2R) in comparison with standard agonist orexin-A together with their blood-brain barrier permeability and cytotoxicity. We can conclude that the studied compounds possess an affinity towards the OX2R. However, the compounds do not have intrinsic activity and act as the antagonists of this receptor. It was shown that L4 was the most potent antagonistic ligand to orexin A and displayed an IC50 of 2.2 mu M, offering some promise mainly for the treatment of insomnia.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/GA17-08596S" target="_blank" >GA17-08596S: Novel therapeutic approaches in narcolepsy</a><br>

Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecules

ISSN

1420-3049

e-ISSN

—

Volume of the periodical

23

Issue of the periodical within the volume

11

Country of publishing house

CH - SWITZERLAND

Number of pages

14

Pages from-to

1-14

UT code for WoS article

000451641900198

EID of the result in the Scopus database

2-s2.0-85056512882