Porro, Alessandro ; Armano, Edoardo ; Brandalise, Federico ; Appiani, Rebecca ; Beltrame, Monica ; Saponaro, Andrea ; Dallanoce, Clelia ; Nakajo, Koichi ; Ryu, Kaei ; Leone, Roberta ; Thiel, Gerhard ; Pallavicini, Marco ; Moroni, Anna ; Bolchi, Cristiano (2024)
A photoactivatable version of ivabradine enables light-induced block of HCN current in vivo.
In: Journal of medicinal chemistry, 67 (18)
doi: 10.1021/acs.jmedchem.4c01047
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
Therapeutic drugs, whose bioactivity is hindered by a photoremovable cage, offer the advantage of spatiotemporal confinement of their action to the target diseased tissue with improved bioavailability and efficacy. Here, we have applied such an approach to ivabradine (IVA), a bradycardic agent indicated for angina pectoris and heart failure, acting as a specific HCN channel blocker. To overcome the side effects due to its poor discrimination among HCN channel subtypes (HCN1-4), we prepared a caged version of IVA linked to a photocleavable bromoquinolinylmethyl group (BHQ-IVA). We show that upon illumination with blue light (440 nm), BHQ-IVA releases active IVA that blocks HCN channel currents and exerts a bradycardic effect . Both BHQ-IVA and the cage are inactive. Caging is stable in aqueous medium and in the dark, and it does not impair aqueous solubility and cell permeation, indispensable for IVA activity. This approach allows for bypassing the poor subtype-specificity of IVA, expanding its prescription to HCN-related diseases besides cardiac.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Porro, Alessandro ; Armano, Edoardo ; Brandalise, Federico ; Appiani, Rebecca ; Beltrame, Monica ; Saponaro, Andrea ; Dallanoce, Clelia ; Nakajo, Koichi ; Ryu, Kaei ; Leone, Roberta ; Thiel, Gerhard ; Pallavicini, Marco ; Moroni, Anna ; Bolchi, Cristiano |
| Art des Eintrags: | Bibliographie |
| Titel: | A photoactivatable version of ivabradine enables light-induced block of HCN current in vivo |
| Sprache: | Englisch |
| Publikationsjahr: | 5 September 2024 |
| Verlag: | ACS Publications |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Journal of medicinal chemistry |
| Jahrgang/Volume einer Zeitschrift: | 67 |
| (Heft-)Nummer: | 18 |
| DOI: | 10.1021/acs.jmedchem.4c01047 |
| Kurzbeschreibung (Abstract): | Therapeutic drugs, whose bioactivity is hindered by a photoremovable cage, offer the advantage of spatiotemporal confinement of their action to the target diseased tissue with improved bioavailability and efficacy. Here, we have applied such an approach to ivabradine (IVA), a bradycardic agent indicated for angina pectoris and heart failure, acting as a specific HCN channel blocker. To overcome the side effects due to its poor discrimination among HCN channel subtypes (HCN1-4), we prepared a caged version of IVA linked to a photocleavable bromoquinolinylmethyl group (BHQ-IVA). We show that upon illumination with blue light (440 nm), BHQ-IVA releases active IVA that blocks HCN channel currents and exerts a bradycardic effect . Both BHQ-IVA and the cage are inactive. Caging is stable in aqueous medium and in the dark, and it does not impair aqueous solubility and cell permeation, indispensable for IVA activity. This approach allows for bypassing the poor subtype-specificity of IVA, expanding its prescription to HCN-related diseases besides cardiac. |
| ID-Nummer: | pmid:39238314 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Biologie der Algen und Protozoen |
| Hinterlegungsdatum: | 09 Sep 2024 12:05 |
| Letzte Änderung: | 07 Okt 2024 07:08 |
| PPN: | 521290511 |
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