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dc.contributor.authorKaczor Agnieszka A
dc.contributor.authorSilva Andrea G
dc.contributor.authorLoza Maria I
dc.contributor.authorKolb Peter
dc.contributor.authorCastro Marián
dc.contributor.authorPoso Antti
dc.date.accessioned2018-10-16T08:24:29Z
dc.date.available2018-10-16T08:24:29Z
dc.date.issued2016
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/7053
dc.description.abstractStructure‐based virtual screening using a D2 receptor homology model was performed to identify dopamine D2 receptor ligands as potential antipsychotics. From screening a library of 6.5 million compounds, 21 were selected and were subjected to experimental validation. From these 21 compounds tested, ten D2 ligands were identified (47.6 % success rate, among them D2 receptor antagonists, as expected) that have additional affinity for other receptors tested, in particular 5‐HT2A receptors. The affinity (Ki values) of the compounds ranged from 58 nm to about 24 μm. Similarity and fragment analysis indicated a significant degree of structural novelty among the identified compounds. We found one D2 receptor antagonist that did not have a protonatable nitrogen atom, which is a key structural element of the classical D2 pharmacophore model necessary for interaction with the conserved Asp(3.32) residue. This compound exhibited greater than 20‐fold binding selectivity for the D2 receptor over the D3 receptor. We provide additional evidence that the amide hydrogen atom of this compound forms a hydrogen bond with Asp(3.32), as determined by tests of its derivatives that cannot maintain this interaction.
dc.language.isoenglanti
dc.publisherWiley-Blackwell
dc.relation.ispartofseriesCHEMMEDCHEM
dc.relation.urihttp://dx.doi.org/10.1002/cmdc.201500599
dc.rightsAll rights reserved
dc.titleStructure-Based Virtual Screening for Dopamine D2 Receptor Ligands as Potential Antipsychotics
dc.description.versionfinal draft
dc.contributor.departmentSchool of Pharmacy, Activities
uef.solecris.id40119108en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© John Wiley & Sons Ltd
dc.relation.doi10.1002/cmdc.201500599
dc.description.reviewstatuspeerReviewed
dc.format.pagerange718-729
dc.relation.issn1860-7179
dc.relation.issue7
dc.relation.volume11
dc.rights.accesslevelopenAccess
dc.type.okmA1
uef.solecris.openaccessEi


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