Development of a first-in-class O-GlcNAc transferase (OGT) inhibitor

化学技术研究人员开发小分子和筛选方法，其他科学家可以使用这些方法来追求治疗开发的创新。O-GlcNAc转移酶（OGT）是催化O-GlcNAc残基附着到细胞核和细胞质蛋白上的重要酶，包括激酶、转录因子、组蛋白和许多其他蛋白质，这些蛋白质反过来调节许多细胞过程。o - glcn酰化仍然没有得到很好的理解，而OGT的小分子抑制剂将成为解剖细胞中这一重要酶功能的关键工具。我们与哈佛大学Walker实验室合作，开发了一种新型的小分子OGT抑制剂，并在几种不同的哺乳动物细胞系中验证了其活性，而不影响细胞表面N-或o -链聚糖的合成。我们正在继续优化这种药物，并正在寻求使用这种OGT生物学探针进行多次合作，以描述其在多种细胞系和疾病环境中的作用。

Chemical Technology researchers develop small molecule and screening approaches that other scientists can use to pursue innovations in therapeutic development. O-GlcNAc transferase (OGT) is an essential enzyme that catalyzes the attachment of O-GlcNAc residues to nuclear and cytoplasmic proteins including kinases, transcription factors, histones and many other proteins which, in turn, regulate numerous cellular processes. O-GlcNAcylation is still not well understood, and small molecule inhibitors of OGT will be a key tool for the dissecting of this important enzymes function in the cell. Working with the Walker lab (Harvard), we have developed a novel small molecule OGT inhibitor and validated its activity in several different mammalian cell lines without affecting synthesis of cell surface N- or O-linked glycans. We are continuing to optimize this agent and are pursuing numerous collaborations using this probe of OGT biology to delineate its role in multiple cell lines and disease settings.