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Ion Channels as Therapeutic Target: Drug Design and Pharmacological Investigation (3rd Edition)

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 1203

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Dipartimento Neurofarba, Università degli Studi di Firenze, Via U. Schiff, 6, Polo Scientifico, 50019 Sesto Fiorentino, Italy
Interests: heterocyclic nitrogen compounds; pyrazolo condensed compounds; synthesis; gabaa receptor subtype; human neutrophil elastase inhibitors; medicinal chemistry
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Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue “Ion Channels as Therapeutic Target: Drug Design and Pharmacological Investigation”.

The targeting of ion channels represents a strategy for the treatment of several pathologies since they are responsible for ion fluxes across membranes and contribute to maintaining cellular functions in central and peripheral tissues. The ion channels include two principal types of membrane proteins:

  1. Ligand-gated ion channels (LGICs), opened by neurotransmitters or ligands that bind the orthosteric or allosteric sites involved in the overall fast synaptic transmission in the nervous system;
  2. Voltage-gated ion channels, opened or closed by a change in the electrical gradient across the membrane.

Ion channels are very intriguing targets, and the development of new techniques elucidating the structures of these channels (e.g., cryo-EM) contributes to the design of new potential therapeutic agents for the treatment of neurological and neurodegenerative diseases, cancer, metabolic syndrome, and pain.

This Special Issue, titled “Ion Channels as Therapeutic Target: Drug Design and Pharmacological Investigation”, aims to collect contributions related to the drug design, molecular modeling, pharmacological investigation, and therapeutic applications of ion channel ligands.

Dr. Gabriella Guerrini
Guest Editor

Manuscript Submission Information

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Keywords

  • LGIC
  • voltage-gated ion channel
  • other ion channels
  • biological studies
  • molecular modeling
  • drug design
  • synthesis

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Published Papers (1 paper)

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Review

20 pages, 1667 KB  
Review
The Two-Pore Channel 2 in Human Physiology and Diseases: Functional Characterisation and Pharmacology
by Laura Lagostena, Velia Minicozzi, Martina Meucci, Antonella Gradogna, Stefan Milenkovic, Fioretta Palombi, Matteo Ceccarelli, Antonio Filippini and Armando Carpaneto
Int. J. Mol. Sci. 2025, 26(19), 9708; https://doi.org/10.3390/ijms26199708 - 6 Oct 2025
Viewed by 1035
Abstract
Two-pore channel 2 (TPC2) is a member of the endolysosomal ion channel family, playing critical roles in intracellular calcium signaling and endomembrane dynamics. This review provides an in-depth analysis of TPC2, covering its structural and functional properties, physiological roles, and involvement in human [...] Read more.
Two-pore channel 2 (TPC2) is a member of the endolysosomal ion channel family, playing critical roles in intracellular calcium signaling and endomembrane dynamics. This review provides an in-depth analysis of TPC2, covering its structural and functional properties, physiological roles, and involvement in human diseases. We discuss current experimental approaches to studying TPC2, including heterologous expression in plant vacuoles and computational modeling strategies. Particular emphasis is placed on the structural determinants of ion permeation, with a focus on the selectivity filter and the central cavity’s influence on channel kinetics. Furthermore, we explore emerging roles of TPC2 in viral infections, particularly SARS-CoV-2, and in cancer, including melanoma progression and neoangiogenesis. The inhibitory potential of natural compounds, such as naringenin, is also examined. By offering a comprehensive overview of current knowledge and methodologies, this review underscores the potential of TPC2 as a promising pharmacological target in both infectious and neoplastic diseases. Full article
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