Emerging biologic modalities for targeted protein degradation.

Alana G Caldwell, Harshil Parmar, Xiaoyu Zhang

Abstract readReview

In one paragraph

Review in The Journal of biological chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Alana G CaldwellInterdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, Illinois, USA.

Harshil ParmarDepartment of Chemistry, Northwestern University, Evanston, Illinois, USA.

Xiaoyu ZhangInterdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, Illinois, USA; Department of Chemistry, Northwestern University, Evanston, Illinois, USA; Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA; Center for Human Immunobiology, Northwestern University, Chicago, Illinois, USA; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois, USA. Electronic address: zhang@northwestern.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

ProteinsProteolysisAnimalsHumansPeptidesProteasome Endopeptidase ComplexProteolysis Targeting ChimeraUbiquitinUbiquitin-Protein LigasesPeptidesProteasome Endopeptidase ComplexProteinsProteolysis Targeting ChimeraUbiquitinUbiquitin-Protein Ligasesantibody and nanobody bindersbiologic degradersE3 ubiquitin ligasespeptide-based degraderstargeted protein degradationubiquitin–proteasome system

Identifiers

PMID41651431

DOI10.1016/j.jbc.2026.111248

PMCPMC12962169

What OpenQuestion holds

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LicenceCC BY

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.