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dc.contributor.authorGabrielsen, Mari
dc.contributor.authorKurczab, Rafal
dc.contributor.authorSiwek, Agata
dc.contributor.authorWolak, Malgorzata
dc.contributor.authorRavna, Aina Westrheim
dc.contributor.authorKristiansen, kurt
dc.contributor.authorKufareva, Irina
dc.contributor.authorAbagyan, Ruben
dc.contributor.authorNowak, Gabriel
dc.contributor.authorChilmonczyk, Zdzislaw
dc.contributor.authorSylte, Ingebrigt
dc.contributor.authorBojarski, Andrzej J.
dc.date.accessioned2022-10-18T09:16:29Z
dc.date.available2022-10-18T09:16:29Z
dc.date.issued2014-02-12
dc.description.abstractThe serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) plays an essential role in the termination of serotonergic neurotransmission by removing 5-HT from the synaptic cleft into the presynaptic neuron. It is also of pharmacological importance being targeted by antidepressants and psychostimulant drugs. Here, five commercial databases containing approximately 3.24 million drug-like compounds have been screened using a combination of two-dimensional (2D) fingerprint-based and threedimensional (3D) pharmacophore-based screening and flexible docking into multiple conformations of the binding pocket detected in an outward-open SERT homology model. Following virtual screening (VS), selected compounds were evaluated using in vitro screening and full binding assays and an in silico hit-to-lead (H2L) screening was performed to obtain analogues of the identified compounds. Using this multistep VS/H2L approach, 74 active compounds, 46 of which had Ki values of ≤1000 nM, belonging to 16 structural classes, have been identified, and multiple compounds share no structural resemblance with known SERT binders.en_US
dc.identifier.citationGabrielsen M, Kurczab R, Siwek A, Wolak M, Ravna aw, Kristiansen k, Kufareva I, Abagyan R, Nowak G, Chilmonczyk Z, Sylte IS, Bojarski AJ. Identification of novel serotonin transporter compounds by virtual Screening. Journal of Chemical Information and Modeling. 2014;54(3):933-943en_US
dc.identifier.cristinIDFRIDAID 1166572
dc.identifier.doi10.1021/ci400742s
dc.identifier.issn1549-9596
dc.identifier.issn1549-960X
dc.identifier.urihttps://hdl.handle.net/10037/27062
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.journalJournal of Chemical Information and Modeling
dc.relation.projectIDNotur/NorStore: NN2978Ken_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holder© 2014 American Chemical Societyen_US
dc.titleIdentification of novel serotonin transporter compounds by virtual Screeningen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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