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| Title | Discovery of membrane channel modulators via DNA encoded library screening using native like membrane protein nanoparticles. |
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| Journal, issue, pages | Sci Rep, Year 2026 |
| Publish date | Jun 15, 2026 |
 Authors | Francesco V Reddavide / Trine L Toft-Bertelsen / Ieva Drulyte / Aspen Rene Gutgsell / Dzung Nguyen / Sara Bonetti / Katerina Vafia / Anne-Sophie Tournillon / Stephan Heiden / Daniel Grosser / Katarina Iric / Veronica Diez / Nanna MacAulay / Stefan Geschwindner / Michael Thompson / Jens Frauenfeld / Robin Löving /      |
| PubMed Abstract | Developing novel drugs against membrane proteins is a major challenge in drug discovery due to the difficulty of stabilizing these targets for high-throughput screenings. Pannexin 1 (PANX1) is a ...Developing novel drugs against membrane proteins is a major challenge in drug discovery due to the difficulty of stabilizing these targets for high-throughput screenings. Pannexin 1 (PANX1) is a membrane channel protein involved in various physiological and pathological processes, making it a promising target for drug discovery. However, efforts to develop PANX1-targeting therapeutics have been hindered by the inherent challenges of stabilizing the protein channel and conducting effective pharmacological screening. Here, we report a proof-of-concept workflow that integrates the Salipro lipid nanoparticle platform with DNA-Encoded Library screenings in a detergent-free format. In this case study, the Salipro DirectMX method was used to generate functional PANX1 nanoparticles for drug discovery and characterisation. Using a high-stringency selection strategy and computational approaches, we identified a specific set of candidate compounds with selective PANX1 enrichment. Surface Plasmon Resonance analysis confirmed the identification of hit compounds. Cryo-Electron Microscopy of the Salipro-PANX1-Compound complex provided structural insights into a potential compound binding site. Electrophysiological recordings in PANX1-expressing Xenopus laevis oocytes demonstrated dose-dependent inhibition of PANX1-mediated ion conductance by the compounds. These findings establish a robust workflow for ligand discovery against challenging membrane protein targets and provide novel chemical starting points for the development of PANX1 modulators. |
 External links | Sci Rep / PubMed:42298013 |
| Methods | EM (single particle) |
| Resolution | 4.5 Å |
| Structure data |  EMDB-56448: Cryo-EM structure of mouse Pannexin 1 in complex with a ligand |
| Source |
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Mus musculus (house mouse)