NPC/MIPE Toxicity Screen of IDH1 Inhibitors against Cholangiocarcinoma Cell Lines

该项目旨在通过检测这些小分子对ICC突变细胞系的毒性，将已批准的药物和其他具有明确作用机制的小分子重新用于IDH1抗癌适应症。

This project aims to repurpose approved drugs and other small molecules with well-characterized mechanisms of action for IDH1 anticancer indications by examining toxicity of these small molecules against ICC mutant cell lines. During this period, the project team screened NCGC's small molecule libraries, and identified a number of hit demonstrating selective toxicity against IDH1 mutant cell lines. Focusing on selected candidates, medicinal chemistry optimization has led to improved physiochemical and therapeutic properties, with the ultimate goal of developing an orally available pre-clinical candidate. Advanced characterization of these molecules is underway to further profile their activity and the mechanism of action responsible for the selective lethality in the context of IDH1 mutant ICC cell lines.