Membrane ubiquitin ligases targeting protein degradation

The present invention relates to a heterobifunctional molecule comprising a first binding domain and a second binding domain wherein i) the first binding domain is capable of specifically binding to a transmembrane E3 ubiquitin ligase; and ii) the second binding domain is capable of specifically binding to a transmembrane protein wherein the heterobifunctional molecule binds simultaneously to a transmembrane E3 ubiquitin ligase and a transmembrane protein resulting in ubiquitination and internalization of the transmembrane protein. The invention also relates to the use of the heterobifunctional molecule for the treatment of a disease wherein preferably the disease is at least one of cancer, an autoimmune disease, an inflammatory disease, an infectious disease and a genetic disease. 本发明涉及一种包含第一结合结构域和第二结合结构域的异双功能分子，其中，i)该第一结合结构域能够与跨膜E3泛素连接酶特异性结合；并且ii)该第二结合结构域能够与跨膜蛋白特异性结合，其中，该异双功能分子同时与跨膜E3泛素连接酶和跨膜蛋白结合，导致跨膜蛋白泛素化和内化。本发明还涉及该异双功能分子用于治疗疾病的用途，其中优选地，该疾病是癌症、自身免疫性疾病、炎症性疾病、传染性疾病和遗传性疾病中的至少一种。