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

IDH1抑制剂对胆管癌细胞系的NPC/MIPE毒性筛选

• 批准号: 10255281
• 负责人: Min Shen
• 金额: $ 30.57万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10255281
• 关键词: Acute Myelocytic Leukemia; Biliary Tract Cancer; Cell Line; Cholangiocarcinoma; Enzymes; Genetic; Glioma; Goals; Intrahepatic Cholangiocarcinoma; Isocitrate Dehydrogenase; Lesion; Malignant Neoplasms; Metabolic; Mutate; Mutation; Nuclear Pore Complex; Oral; Patients; Pharmaceutical Chemistry; Pharmaceutical Preparations; Property; Survival Rate; Therapeutic; Toxic effect; Unresectable; anti-cancer; carcinogenesis; clinical candidate; improved; inhibitor/antagonist; mutant; pre-clinical; small molecule; small molecule libraries; tumor

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 ETB'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.

该项目的目的是通过检查这些小分子对ICC突变细胞系的毒性，以重新利用批准的药物和其他小分子，并具有良好的IDH1抗癌指示作用机理。 在此期间，项目团队筛选了ETB的小分子文库，并确定了许多命中，这些命中率证明了针对IDH1突变细胞系的选择性毒性。专注于选定的候选者，药物化学优化已改善了理化和治疗特性，其最终目的是开发口服临床前候选者。这些分子的高级表征正在进行进一步介绍其活性以及在IDH1突变ICC细胞系中选择性致死性的作用机理。