Abstract
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.
Original language | English |
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Pages (from-to) | 627-632 |
Number of pages | 6 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 10 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 11 2019 |
Keywords
- ASICs
- cancer
- CNS
- drug discovery
- ion channels
- PNS
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry