Identification of brain-permeant small molecule modulators of GAL1R receptor

阿片受体是大多数强效镇痛药（如吗啡）的主要靶点。然而，严重的副作用，如依赖和呼吸抑制与该受体有关。这个项目团队的成员已经报告了大量的位于腹侧被盖区（VTA）的多阿片受体（MOR）与丙氨酸Gal1受体（GAL1R）形成异聚体，调节多巴胺细胞功能。因此，这些morr - gal1r异构体可能是治疗阿片类药物使用障碍的潜在靶点。

The mu opioid receptor is the major target of most potent analgesics (e.g. morphine). However, severe side effects such as dependence and respiratory depression have been associated with this receptor. Members of this project team have reported that a significant population of mu-opioid receptors (MOR) localized in the ventral tegmental area (VTA) form heteromers with galanin Gal1 receptors (GAL1R) which modulate dopamine cell function. As such, these MOR-GAL1R heteromers may represent a potential target for the treatment of opioid use disorder. The project team intends to screen in-house libraries to identify small molecules modulating GAL1R receptor. The hits will be profiled for selectivity, and medicinal chemistry will be undertaken for select molecules to further improve their efficacy and potency.