Repurposing dopamine D3 receptor fluorescent ligands for D2 receptor
- 1University of Tartu, Institute of Chemistry
Abstract
The dopamine D2 receptor is a principal target of antipsychotic and antiparkinsonian drugs, yet well-characterized fluorescent ligands for the D2 receptor remain scarce compared with its relative, the D3 receptor. Here we show that fluorescent ligands developed for the D3 subtype can be repurposed as tools for studying the D2 receptor pharmacology. Using a machine-learning-assisted, live-cell fluorescence microscopy assay, we screened twelve fluorescent probes and identified eight ligands that bound specifically to the D2 receptor at 10 nM. Four ligands exhibited classical saturable binding, yielding Kd in the nanomolar range, whereas the remaining probes displayed unsaturated, time-dependent binding profiles. Kinetic analyses revealed substantial differences in association and dissociation behavior, highlighting the importance of time-resolved measurements. Competition binding with dopamine and haloperidol yielded affinity estimates consistent with literature values. These results expand the toolkit of validated D2 receptor fluorescent probes and support cross-receptor repurposing as a strategy for fluorescent ligand development.
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BibTeX
@misc{ots2026repurposing,
title = {{Repurposing dopamine D3 receptor fluorescent ligands for D2 receptor}},
author = {K. Ots and T. Laasfeld and K. Hollo and M. Ilisson and S. Ortigueira Noya and F. Grassl and D. Tousi and H.-R. Allas and M. Majellaro and E. Enkvist and M. R. Heinrich and E. Sotelo and A. Allikalt},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.756687},
url = {https://www.biorxiv.org/content/10.64898/2026.10.07.756687v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Repurposing dopamine D3 receptor fluorescent ligands for D2 receptor
AU - K. Ots
AU - T. Laasfeld
AU - K. Hollo
AU - M. Ilisson
AU - S. Ortigueira Noya
AU - F. Grassl
AU - D. Tousi
AU - H.-R. Allas
AU - M. Majellaro
AU - E. Enkvist
AU - M. R. Heinrich
AU - E. Sotelo
AU - A. Allikalt
PY - 2026
DA - 2026/10/07
PB - bioRxiv
DO - 10.64898/2026.10.07.756687
UR - https://www.biorxiv.org/content/10.64898/2026.10.07.756687v1
AB - The dopamine D2 receptor is a principal target of antipsychotic and antiparkinsonian drugs, yet well-characterized fluorescent ligands for the D2 receptor remain scarce compared with its relative, the D3 receptor. Here we show that fluorescent ligands developed for the D3 subtype can be repurposed as tools for studying the D2 receptor pharmacology. Using a machine-learning-assisted, live-cell fluorescence microscopy assay, we screened twelve fluorescent probes and identified eight ligands that bound specifically to the D2 receptor at 10 nM. Four ligands exhibited classical saturable binding, yielding Kd in the nanomolar range, whereas the remaining probes displayed unsaturated, time-dependent binding profiles. Kinetic analyses revealed substantial differences in association and dissociation behavior, highlighting the importance of time-resolved measurements. Competition binding with dopamine and haloperidol yielded affinity estimates consistent with literature values. These results expand the toolkit of validated D2 receptor fluorescent probes and support cross-receptor repurposing as a strategy for fluorescent ligand development.
ER -