Identification of brain-permeant small molecule modulators of GAL1R receptor

μ阿片受体是最有效的镇痛剂（例如吗啡）的主要靶标。然而，严重的副作用，如依赖和呼吸抑制已与这种受体。该项目团队的成员报告称，位于腹侧被盖区（VTA）的大量μ阿片受体（莫尔）与甘丙肽Gal 1受体（GAL 1 R）形成异聚体，调节多巴胺细胞功能。因此，这些MOR-GAL 1 R异聚体可能是治疗阿片类药物使用障碍的潜在靶点。 项目团队打算筛选内部文库，以鉴定调节GAL 1 R受体的小分子。将对命中进行选择性分析，并将对选择的分子进行药物化学，以进一步提高其功效和效力。

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.