Bristol Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
Bristol Myers Squibb, 10300 Campus Point Drive, San Diego, California 92121, United States.
J Med Chem. 2024 Sep 26;67(18):15996-16001. doi: 10.1021/acs.jmedchem.4c01289. Epub 2024 Sep 4.
Herein, we discuss advancements in the field of a unique class of antibody-drug conjugates (ADCs) named molecular glue-antibody conjugate (MAC). ADCs traditionally employ cytotoxic agents as payloads, and this approach has been used in all approved ADCs to treat cancer. Complementary to this approach, proteolysis targeting chimera (PROTAC) degrader antibody conjugates (DACs) provide a unique opportunity to deliver these bifunctional agents to tumors by using antibodies as a delivery mechanism to overcome the bioavailability issues encountered by PROTAC payloads. Recently, a cereblon binding monovalent degrader called molecular glues has been used in new ADCs that we have coined the term molecular-glue antibody conjugates (MACs). In this article, we intend to review advancements made in the field of targeted delivery of cereblon-based molecular glue degraders.
在这里，我们讨论了一类独特的抗体药物偶联物 (ADC) 的进展，这些 ADC 被称为分子连接子 - 抗体偶联物 (MAC)。ADC 传统上使用细胞毒性药物作为有效载荷，这种方法已被用于所有批准的 ADC 中以治疗癌症。作为对此方法的补充，蛋白酶体靶向嵌合体 (PROTAC) 降解剂抗体偶联物 (DAC) 通过使用抗体作为递送机制提供了一个独特的机会，将这些双功能药物递送到肿瘤中，以克服 PROTAC 有效载荷遇到的生物利用度问题。最近，一种称为分子连接子的 cereblon 结合单价降解剂已被用于我们称为分子连接子 - 抗体偶联物 (MAC) 的新型 ADC 中。在本文中，我们旨在综述基于 cereblon 的分子连接子降解剂靶向递送方面的进展。
