Work

Emerging biologic modalities for targeted protein degradation

Year: 2026

Type: article

Abstract: Targeted protein degradation (TPD) has emerged as a powerful approach for eliminating disease-associated proteins by harnessing the ubiquitin-proteasome system. Biologic degraders are modular protein chimeras that recruit ubiquitin machinery to target proteins. They offer high specificity, modular design, and the ability to access targets traditionally considered challenging for small-molecule ligands. This review surveys the expanding landscape of biologic TPD modalities, highlighting E3 ligase- and E2 enzyme-based degraders, TRIM-Away and TRIMbody-Away systems, and diverse biologics-based ligands that serve as target-binding components. We also discuss emerging peptide-based strategies, which bridge biologic and synthetic approaches. Finally, we highlight future opportunities to improve biologic degraders and their potential to expand the scope of TPD.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2026.111248

Authors: Alana G. Caldwell, Harshil Parmar, Xiaoyu Zhang

Institutions: Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, International Institute for Nanotechnology, Chemistry of Life Processes Institute

Language: English

Topic: Protein Degradation and Inhibitors

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,430