@article{
author = "Saretz, Stefan and Basset, Gabriele and Useini, Liridona and Laube, Markus and Pietzsch, Jens and Drača, Dijana and Maksimović-Ivanić, Danijela and Trambauer, Johannes and Steiner, Harald and Hey-Hawkins, Evamarie",
year = "2021",
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.",
publisher = "MDPI AG",
journal = "Molecules",
title = "Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue",
number = "10",
volume = "26",
doi = "10.3390/molecules26102843",
pages = "2843"
}