Xiaochu Ba, Mahzad Dehghany, Deborah S. Mortensen and Natalie Holmberg-Douglas
RSC Med. Chem., 2026,17, 80-104
Abstract
This review summarizes recent synthetic advances for glutarimide scaffolds enabling cereblon-mediated targeted protein degradation.
Yuka Amako, Saki Ichikawa, Hannah C. Lloyd, N. Connor Payne, Zhi Lin, Andrew S. Boghossian, Matthew G. Rees, Melissa M. Ronan, Jennifer A. Roth, Qian Zhu, Bogdan Budnik, Ralph Mazitschek and Christina M. Woo
Chem. Sci., 2025,16, 11519-11529
Abstract
A systematic investigation of cyclic imide stereoisomers in small molecules, peptides, and proteins, examining their racemization, CRBN engagement, ternary complex formation in vitro, and resulting degradation outcomes in cells.
Radosław P. Nowak, Jianwei Che, Silas Ferrao, Nikki R. Kong, Hu Liu, Breanna L. Zerfas and Lyn H. Jones
RSC Med. Chem., 2023,14, 501-506
Abstract
Ternary complex structural knowledge enabled elucidation of structure–degradation relationships that will assist the future design of cereblon modulators that avoid GSPT1 toxicity.
Radosław P. Nowak, Leah Ragosta, Fidel Huerta, Hu Liu, Scott B. Ficarro, Justin T. Cruite, Rebecca J. Metivier, Katherine A. Donovan, Jarrod A. Marto, Eric S. Fischer, Breanna L. Zerfas and Lyn H. Jones
RSC Chem. Biol., 2023,4, 906-912
From themed collection:
RSC Chemical Biology – Editors Choice Collection 2023
Abstract
The first covalent cereblon-based PROTAC was developed using a fluorosulfate warhead to site-specifically engage His353 in the sensor loop of the E3 ligase, yielding a degrader with prolonged pharmacodynamics.
Breanna L. Zerfas, Yingpeng Liu, Jianwei Che, Katherine A. Donovan, John M. Hatcher, Fidel Huerta, Rebecca J. Metivier, Radosław P. Nowak, Leah Ragosta, Tiffany Tsang, Eric S. Fischer and Lyn H. Jones
RSC Med. Chem., 2025,16, 2460-2466
From themed collection:
Kinases
Abstract
The first degrader of an ER-resident protein (IRE1α) is described with properties more akin to a molecular glue than a traditional PROTAC, thus challenging the dogma of categorizing degrader modalities based on their physicochemical features.