Identification of Inhibitors of human Galactokinase (GALK) for the treatment of Galactosemia

该项目旨在发现和开发Galk的抑制剂，作为治疗经典半乳糖血症的潜在新疗法。在此期间，合作团队继续开展其持续的药物化学活动，以(1)提高铅系列的Galk抑制活性，(2)提高备份系列的Galk抑制活性，(2)改善BBB暴露。感兴趣的化合物已经被推进到基于细胞的分析和动物模型中，以进一步表征它们的细胞活性。此外，一种基于细胞的Gal1-p LC/MS分析已经在开发中，以实现对细胞内代谢物的直接测量，并提供一个急需的靶向活性的标记。发表了一篇医学论文，展示了基于结构的药物设计，以提高先导化学系列的效力。

This project aims to identify and develop inhibitors of GALK as a potential novel therapy for Classic Galactosemia. During this period, the collaborative team continued with its ongoing medicinal chemistry campaign to (1) improve GALK inhibitory activity on the lead series, (2) improve GALK inhibitory activity on the backup series, (2) improve BBB exposure. Compounds of interest have been advanced into cell-based assays and animal models to further characterize their cellular activity. In addition, a cell-based Gal1-p LC/MS assay has been in development to enable direct measurement of the metabolite in cells and provide a much needed marker of on-target activity. A medchem paper was published showcasing structure-based drug design to improve the potency of a the lead chemical series.