dc.date.accessioned | 2021-01-11T19:59:55Z | |
dc.date.available | 2021-01-11T19:59:55Z | |
dc.date.created | 2020-08-13T11:10:58Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Bekker, Roberto Bartholomeus Wilhelmus Fjellaksel, Richard Hjornevik, Trine Nuruddin, Syed Rafique, Waqas Hansen, Jørn H Sundset, Rune Haraldsen, Ira Hebold Riss, Patrick . Discovery of a lead brain-penetrating gonadotropin-releasing hormone receptor antagonist with saturable binding in brain. ChemMedChem. 2020, 15(17), 1624-1628 | |
dc.identifier.uri | http://hdl.handle.net/10852/82097 | |
dc.description.abstract | We report the synthesis, radiosynthesis and biological characterisation of two gonadotropin‐releasing hormone receptor (GnRH−R) antagonists with nanomolar binding affinity. A small library of GnRH−R antagonists was synthesised in 20–67 % overall yield with the aim of identifying a high‐affinity antagonist capable of crossing the blood–brain barrier. Binding affinity to rat GnRH−R was determined by autoradiography in competitive‐binding studies against [125I]buserelin, and inhibition constants were calculated by using the Cheng–Prusoff equation. The radioligands were obtained in 46–79 % radiochemical yield and >95 % purity and with a molar activity of 19–38 MBq/nmol by direct nucleophilic radiofluorination. Positron emission tomography imaging in rat under baseline conditions in comparison to pretreatment with a receptor‐saturating dose of GnRH antagonist revealed saturable uptake (0.1 %ID/mL) into the brain. | |
dc.language | EN | |
dc.publisher | Wiley - VCH Verlag GmbH | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | Discovery of a lead brain-penetrating gonadotropin-releasing hormone receptor antagonist with saturable binding in brain | |
dc.type | Journal article | |
dc.creator.author | Bekker, Roberto Bartholomeus Wilhelmus | |
dc.creator.author | Fjellaksel, Richard | |
dc.creator.author | Hjornevik, Trine | |
dc.creator.author | Nuruddin, Syed | |
dc.creator.author | Rafique, Waqas | |
dc.creator.author | Hansen, Jørn H | |
dc.creator.author | Sundset, Rune | |
dc.creator.author | Haraldsen, Ira Hebold | |
dc.creator.author | Riss, Patrick | |
cristin.unitcode | 185,15,12,62 | |
cristin.unitname | Miljøvitenskap | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1823124 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=ChemMedChem&rft.volume=15&rft.spage=1624&rft.date=2020 | |
dc.identifier.jtitle | ChemMedChem | |
dc.identifier.volume | 15 | |
dc.identifier.issue | 17 | |
dc.identifier.startpage | 1624 | |
dc.identifier.endpage | 1628 | |
dc.identifier.doi | https://doi.org/10.1002/cmdc.202000256 | |
dc.identifier.urn | URN:NBN:no-85007 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1860-7179 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/82097/1/article7201.pdf | |
dc.type.version | PublishedVersion | |