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 |
Autori: | |
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 |
Rivista: | |
Tipologia: | Article (author) |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1021/acsmedchemlett.8b00591 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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