Abstract
The orexin receptors are peptide-sensing G protein-coupled receptors that are intimately linked with regulation of the sleep/wake cycle. We used a recently solved X-ray structure of the orexin receptor subtype 2 in computational docking calculations with the aim to identify additional ligands with unprecedented chemotypes. We found validated ligands with a high hit rate of 29% out of those tested, none of them showing selectivity with respect to the orexin receptor subtype 1. Furthermore, of the higher-affinity compounds examined, none showed any agonist activity. While novel chemical structures can thus be found, selectivity is a challenge owing to the largely identical binding pockets.
Original language | English (US) |
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Pages (from-to) | 11045-11053 |
Number of pages | 9 |
Journal | Journal of Medicinal Chemistry |
Volume | 63 |
Issue number | 19 |
DOIs | |
State | Published - Oct 8 2020 |
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery