The New Frontier: Merging Molecular Glue Degrader and Antibody–Drug Conjugate Modalities To Overcome Strategic ChallengesClick to copy article linkArticle link copied!
- Yam B. Poudel*Yam B. Poudel*E-mail: [email protected]Bristol Myers Squibb, 700 Bay Road, Redwood City, California 94063, United StatesMore by Yam B. Poudel
- Ruchita R. ThakoreRuchita R. ThakoreBristol Myers Squibb, 10300 Campus Point Drive, San Diego, California 92121, United StatesMore by Ruchita R. Thakore
- Eugene P. Chekler*Eugene P. Chekler*E-mail: [email protected]Bristol Myers Squibb, 700 Bay Road, Redwood City, California 94063, United StatesMore by Eugene P. Chekler
Abstract
![Abstract Image](/cms/10.1021/acs.jmedchem.4c01289/asset/images/medium/jm4c01289_0009.gif)
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.
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