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Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue
dc.creator | Saretz, Stefan | |
dc.creator | Basset, Gabriele | |
dc.creator | Useini, Liridona | |
dc.creator | Laube, Markus | |
dc.creator | Pietzsch, Jens | |
dc.creator | Drača, Dijana | |
dc.creator | Maksimović-Ivanić, Danijela | |
dc.creator | Trambauer, Johannes | |
dc.creator | Steiner, Harald | |
dc.creator | Hey-Hawkins, Evamarie | |
dc.date.accessioned | 2021-06-04T11:42:52Z | |
dc.date.available | 2021-06-04T11:42:52Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 1420-3049 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151329/ | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/4250 | |
dc.description.abstract | All over the world, societies are facing rapidly aging populations combined with a growing number of patients suffering from Alzheimer’s disease (AD). One focus in pharmaceutical research to address this issue is on the reduction of the longer amyloid-β (Aβ) fragments in the brain by modulation of γ-secretase, a membrane-bound protease. R-Flurbiprofen (tarenflurbil) was studied in this regard but failed to show significant improvement in AD patients in a phase 3 clinical trial. This was mainly attributed to its low ability to cross the blood–brain barrier (BBB). Here, we present the synthesis and in vitro evaluation of a racemic meta-carborane analogue of flurbiprofen. By introducing the carborane moiety, the hydrophobicity could be shifted into a more favourable range for the penetration of the blood–brain barrier, evident by a logD7.4 value of 2.0. Furthermore, our analogue retained γ-secretase modulator activity in comparison to racemic flurbiprofen in a cell-based assay. These findings demonstrate the potential of carboranes as phenyl mimetics also in AD research. | |
dc.publisher | MDPI AG | |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200007/RS// | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | Molecules | |
dc.subject | Alzheimer | |
dc.subject | Amyloid-β (Aβ) peptide | |
dc.subject | Carborane | |
dc.subject | Flurbiprofen | |
dc.subject | Phenyl mimetic | |
dc.subject | Small molecule | |
dc.subject | γ-secretase modulator (GSM) | |
dc.title | Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue | |
dc.type | article | en |
dc.rights.license | BY | |
dcterms.abstract | Стеинер, Харалд; Трамбауер, Јоханнес; Усеини, Лиридона; Бассет, Габриеле; Саретз, Стефан; Хеy-Хаwкинс, Евамарие; Драча, Дијана; Пиетзсцх, Јенс; Лаубе, Маркус; Максимовић-Иванић, Данијела; | |
dc.rights.holder | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. | |
dc.citation.issue | 10 | |
dc.citation.volume | 26 | |
dc.identifier.doi | 10.3390/molecules26102843 | |
dc.identifier.pmid | 34064783 | |
dc.identifier.scopus | 2-s2.0-85106616220 | |
dc.identifier.wos | 000655054800001 | |
dc.citation.apa | Saretz, S., Basset, G., Useini, L., Laube, M., Pietzsch, J., Drača, D., et al. (2021). Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue. Molecules, 26(10), 2843. | |
dc.citation.vancouver | Saretz S, Basset G, Useini L, Laube M, Pietzsch J, Drača D, Maksimović-Ivanić D, Trambauer J, Steiner H, Hey-Hawkins E. Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue. Molecules. 2021;26(10):2843. | |
dc.citation.spage | 2843 | |
dc.type.version | publishedVersion | |
dc.identifier.fulltext | https://radar.ibiss.bg.ac.rs/bitstream/id/8504/molecules-26-02843.pdf | |
dc.citation.rank | M22 |