Disclosed are prodrugs of cytotoxic anthracyclines (such as doxorubicin) and other therapeutic agents that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of cytotoxic and other agents to FAP- expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, fibrosis, and inflammation.
本文披露了细胞毒性
蒽环类似物(如
阿霉素)和其他治疗剂的前药,这些前药通过成纤维细胞激活蛋白(
FAP)选择性地被切割和激活。这些前药可用于将细胞毒性和其他药物靶向输送至表达
FAP的组织,包括癌症(如实体肿瘤)。还提供了包含这些前药的药物化合物,以及使用这些前药治疗由
FAP上调引起的疾病的方法,例如癌症、纤维化和炎症。