The chronological evolution of fluorescent GPCR probes for bioimaging

Novel far-red fluorescent 1,4-dihydropyridines for L-type calcium channels imaging

“…One of the main challenges of developing novel fluorescent ligands is to retain affinity and potency for their target in a biological context. 17,24,[30][31][32] In particular, far-red fluorescent dyes often consist of large lipophilic molecules, with high molecular mass and steric hindrance, which explains why many fluorescent ligands derived from these fluorophores and a pharmacophore show low affinity for the target. 32 A rigorous pharmacological characterization is therefore critical, as its affinity and/or pharmacological effect may differ significantly from that of the original pharmacophore.…”

“…17,24,[30][31][32] In particular, far-red fluorescent dyes often consist of large lipophilic molecules, with high molecular mass and steric hindrance, which explains why many fluorescent ligands derived from these fluorophores and a pharmacophore show low affinity for the target. 32 A rigorous pharmacological characterization is therefore critical, as its affinity and/or pharmacological effect may differ significantly from that of the original pharmacophore. 31 To achieve this, we carried out the pharmacological evaluation of FluoDiPine1-13 (Scheme 1C) via three distinct approaches: i) qualitative determination via live-cell calcium imaging in differentiated human mesoangioblastderived myotubes; ii) IC50 determination via whole cell patch-clamp in transfected HEK 293 cells and iii) IC50 determination via live-cell calcium imaging in SH-SY5Y cells.…”

Novel far-red fluorescent 1,4-dihydropyridines for L-type calcium channel imaging

“…One of the main challenges of developing novel fluorescent ligands is to retain affinity and potency for their target in a biological context. 22,32,[40][41][42] In particular, far-red fluorescent dyes often consist of large lipophilic molecules, with high molecular mass and steric hindrance, which explains why many fluorescent ligands derived from these fluorophores and a pharmacophore show low affinity for https://doi.org/10.26434/chemrxiv-2023-5z0lq-v2 ORCID: https://orcid.org/0000-0002-9632-2906 Content not peer-reviewed by ChemRxiv. License: CC BY-NC-ND 4.0 the target.…”

“…License: CC BY-NC-ND 4.0 the target. 42 A rigorous pharmacological characterization is therefore critical, as its affinity and/or pharmacological effect may differ significantly from that of the original pharmacophore. 41 The deliberate choice of employing three cell lines expressing different LTCC isoforms stems from the pan-LTCC blocker properties inherent in the 1,4-DHP scaffold.…”

“…This is noteworthy considering how difficult it is to retain potency for the target when attaching far-red dyes to small-molecule pharmacophores. 42 Confocal microscopy in fixed transfected cells.…”