Acid-sensing ion channels (ASICs) are a family of ion channels permeable to cations and largely responsible for the onset of acid-evoked ion currents both in neurons and in different types of cancer cells, thus representing a potential target for drug discovery. Owing to the limited attention ASIC2 has received so far, an exploratory program was initiated to identify ASIC2 inhibitors using diminazene, a known pan-ASIC inhibitor, as a chemical starting point for structural elaboration. The performed exploration enabled the identification of a novel series of ASIC2 inhibitors. In particular, compound 2u is a brain penetrant ASIC2 inhibitor endowed with an optimal pharmacokinetic profile. This compound may represent a useful tool to validate in animal models in vivo the role of ASIC2 in different neurodegenerative central nervous system pathologies.
Identification of Isoform 2 Acid-Sensing Ion Channel Inhibitors as Tool Compounds for Target Validation Studies in CNS / L.I. Bencheva, M. De Matteo, L. Ferrante, M. Ferrara, A. Prandi, P. Randazzo, S. Ronzoni, R. Sinisi, P. Seneci, V. Summa, M. Gallo, M. Veneziano, A. Cellucci, N. Mazzocchi, A. Menegon, R. Di Fabio. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 10:4(2019 Feb), pp. 627-632.
|Titolo:||Identification of Isoform 2 Acid-Sensing Ion Channel Inhibitors as Tool Compounds for Target Validation Studies in CNS|
|Parole Chiave:||ASICs; ion channels; drug discovery; CNS; PNS; cancer|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
Settore CHIM/06 - Chimica Organica
Settore MED/26 - Neurologia
|Data di pubblicazione:||feb-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/acsmedchemlett.8b00591|
|Appare nelle tipologie:||01 - Articolo su periodico|