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Updated: Jan 13, 2026

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps
Published on: July 19, 2024
Mapping ligands for MT1/MT2 and 5-HT2C receptors: Chemotypes, SAR, and polypharmacology
Alban Lepailleur1, Damien Geslin1, Johanna Giovannini1
1Université Caen Normandie, Normandie Univ, CERMN UR4258, F-14000 Caen, France.
None:
Understanding ligand selectivity and efficacy at melatonin (MT1, MT2) and serotonin (5-HT2C) receptors remains a key challenge in central nervous system (CNS) drug discovery. Ligands combining MT1/MT2 agonism with 5-HT2C antagonism are of therapeutic relevance in depression and circadian rhythm disorders. This review provides a comprehensive overview of ligands reported for these receptors in ChEMBL, with an emphasis on compounds evaluated across multiple targets. A pharmacophore-based approach was applied to group ligands by shared features, revealing pharmacomodulations influencing receptor selectivity and polypharmacology. Together, these insights can inspire the rational design of selective or polypharmacological ligands, offering new opportunities for multitarget drug discovery.
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