dc.contributor.author | Betari, Nibal | |
dc.contributor.author | Sahlholm, Kristoffer | |
dc.contributor.author | Ishizuka, Yuta | |
dc.contributor.author | Teigen, Knut | |
dc.contributor.author | Haavik, Jan | |
dc.date.accessioned | 2021-04-30T11:21:40Z | |
dc.date.available | 2021-04-30T11:21:40Z | |
dc.date.created | 2020-10-03T11:06:04Z | |
dc.date.issued | 2020 | |
dc.Published | Future Medicinal Chemistry. 2020, 12 (16), 1461-1474. | |
dc.identifier.issn | 1756-8919 | |
dc.identifier.uri | https://hdl.handle.net/11250/2740581 | |
dc.description.abstract | Aim: Tryptophan hydroxylase 1 (TPH1) catalyzes serotonin synthesis in peripheral tissues. Selective TPH1 inhibitors may be useful for treating disorders related to serotonin dysregulation. Results & methodology: Screening using a thermal shift assay for TPH1 binders yielded Compound 1 (2-(4-methylphenyl)-1,2-benzisothiazol-3(2H)-one), which showed high potency (50% inhibition at 98 ± 30 nM) and selectivity for inhibiting TPH over related aromatic amino acid hydroxylases in enzyme activity assays. Structure–activity relationships studies revealed several analogs of 1 showing comparable potency. Kinetic studies suggested a noncompetitive mode of action of 1, with regards to tryptophan and tetrahydrobiopterin. Computational docking studies and live cell assays were also performed. Conclusion: This TPH1 inhibitor scaffold may be useful for developing new therapeutics for treating elevated peripheral serotonin. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Future Science | en_US |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/deed.no | * |
dc.title | Discovery and biological characterization of a novel scaffold for potent inhibitors of peripheral serotonin synthesis | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2020 The Authors | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.4155/fmc-2020-0127 | |
dc.identifier.cristin | 1836735 | |
dc.source.journal | Future Medicinal Chemistry | en_US |
dc.source.40 | 12 | |
dc.source.14 | 16 | |
dc.source.pagenumber | 1461-1474 | en_US |
dc.identifier.citation | Future Medicinal Chemistry. 2020, 12(16), 1461–1474 | en_US |
dc.source.volume | 12 | en_US |
dc.source.issue | 16 | en_US |