2026-04-20T09:12:38Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/165682024-09-27T08:34:16Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Milani, Gualtiero
author
Budriesi, Roberta
author
Tavazzani, Elisa
author
Cavalluzzi, Maria Maddalena
author
Mattioli, Laura Beatrice
author
Miniero, Daniela Valeria
author
Delre, Pietro
author
Belviso, Benny Danilo
author
Denegri, Marco
author
Cuocci, Corrado
author
Rotondo, Natalie Paola
author
De Palma, Annalisa
author
Gualdani, Roberta
author
Caliandro, Rocco
author
Mangiatordi, Giuseppe Felice
author
Kumawat, Amit
author
Camilloni, Carlo
author
Priori, Silvia G.
author
Lentini, Giovanni
2023-10-16T13:47:20Z
2023-10-16T13:47:20Z
2023-10
Arch Pharm (Weinheim). 2023 Oct;356(10):e2300116.
http://hdl.handle.net/20.500.12105/16568
37460390
10.1002/ardp.202300116
1521-4184
Archiv der Pharmazie
Long QT syndrome (LQTS) is a disorder of cardiac electrophysiology resulting in life-threatening arrhythmias; nowadays, only a few drugs are available for the management of LQTS. Focusing our attention on LQT2, one of the most common subtypes of LQTS caused by mutations in the human ether-à-go-go-related gene (hERG), in the present work, the stereoselectivity of the recently discovered mexiletine-derived urea 8 was investigated on the hERG potassium channel. According to preliminary in silico predictions, in vitro studies revealed a stereoselective behavior, with the meso form showing the greatest hERG opening activity. In addition, functional studies on guinea pig isolated left atria, aorta, and ileum demonstrated that 8 does not present any cardiac or intestinal liability in our ex vivo studies. Due to its overall profile, (R,S)-8 paves the way for the design and development of a new series of compounds potentially useful in the treatment of both congenital and drug-induced forms of LQTS.
eng
hERG stereoselective modulation by mexiletine-derived ureas: Molecular docking study, synthesis, and biological evaluation.
journal article
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hERG stereoselective modulation_Arch Pharm_Weinheim_2023.pdf
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https://repisalud.isciii.es/bitstreams/ed53de8b-f29c-48f8-af5b-8986daa71957/download
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hERG stereoselective modulation_Arch Pharm_Weinheim_2023.pdf.txt