Identification of the Candidate mGlu2 Allosteric Modulator THRX-195518 through In Silico Method and Evaluation of Its Neuroprotective Potential against Glutamate-Induced Neurotoxicity in SH-SY5Y Cell Line

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dc.authorid0000-0001-6759-7735en_US
dc.authorscopusid57197822841en_US
dc.authorwosid-en_US
dc.contributor.authorCanbolat, Fadime
dc.contributor.authorKantarci-Carsibasi, Nigar
dc.contributor.authorIşık, Sevim
dc.contributor.authorShamshir, Suhair Rami Mohammed
dc.contributor.authorGirgin, Münteha
dc.date.accessioned2024-02-20T12:20:04Z
dc.date.available2024-02-20T12:20:04Z
dc.date.issued2024en_US
dc.departmentMeslek Yüksekokulları, Sağlık Hizmetleri Meslek Yüksekokulu, Eczane Hizmetleri Bölümü
dc.description.abstractGlutamate (Glu) toxicity has been an important research topic in toxicology and neuroscience studies. In vitro and in vivo studies have shown that Group II metabotropic Glu2 (mGlu2) activators have cell viability effects. This study aims to determine a candidate ligand with high mGlu2 allosteric region activity among cytotoxicity-safe molecules using the in silico positioning method and to evaluate its cell viability effect in vitro. We investigated the candidate molecule’s cell viability effect on the SH-SY5Y human neuroblastoma cell line by MTT analysis. In the study, LY 379268 (agonist) and JNJ-46281222 (positive allosteric modulator; PAM) were used as control reference molecules. Drug bank screening yielded THRX-195518 (docking score being −12.4 kcal/mol) as a potential novel drug candidate that has a high docking score and has not been mentioned in the literature so far. The orthosteric agonist LY 379268 exhibited a robust protective effect in our study. Additionally, our findings demonstrate that JNJ-46281222 and THRX-195518, identified as activating the mGlu2 allosteric region through in silico methods, preserve cell viability against Glu toxicity. Therefore, our study not only emphasizes the positive effects of this compound on cell viability against Glu toxicity but also sheds light on the potential of THRX-195518, acting as a mGlu2 PAM, based on in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) data, as a candidate drug molecule. These findings underscore the potential utility of THRX-195518 against both neurotoxicity and Central Nervous System (CNS) disorders, providing valuable insights.en_US
dc.identifier.citationCanbolat, F., Kantarcı-Çarşıbası, N., Işık, S., Shamshir, S. R. M., & Girgin, M. (2024). Identification of the Candidate mGlu2 Allosteric Modulator THRX-195518 through In Silico Method and Evaluation of Its Neuroprotective Potential against Glutamate-Induced Neurotoxicity in SH-SY5Y Cell Line. Current Issues in Molecular Biology, 46(1), 788–807. doi: 10.3390/cimb46010051en_US
dc.identifier.doi10.3390/cimb46010051
dc.identifier.endpage807en_US
dc.identifier.issn1467-3037
dc.identifier.issn1467-3045
dc.identifier.issue1en_US
dc.identifier.pmid38248353
dc.identifier.scopus2-s2.0-85183449455
dc.identifier.startpage788en_US
dc.identifier.urihttps://doi.org/10.3390/cimb46010051
dc.identifier.urihttps://hdl.handle.net/20.500.12428/5680
dc.identifier.volume46en_US
dc.identifier.wosWOS:001149269700001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorCanbolat, Fadime
dc.language.isoen
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)en_US
dc.relation.ispartofCurrent Issues in Molecular Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectCell viabilityen_US
dc.subjectMetabotropic glutamate receptoren_US
dc.subjectPositive allosteric modulatoren_US
dc.subjectSH-SY5Yen_US
dc.titleIdentification of the Candidate mGlu2 Allosteric Modulator THRX-195518 through In Silico Method and Evaluation of Its Neuroprotective Potential against Glutamate-Induced Neurotoxicity in SH-SY5Y Cell Line
dc.typeArticle

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