ReviewFrontiers in pharmacology2026
Research progress and future perspectives in proteolysis-targeting chimeras.
Review in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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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.
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.
Who cites it
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteolysis-targeting chimeras (PROTACs) have emerged as a transformative modality within the targeted protein degradation (TPD) landscape, inducing spatial proximity between E3 ubiquitin ligases and proteins of interest (POIs) to hijack the ubiquitin-proteasome system (UPS). Unlike traditional occupancy-driven inhibitors, this catalytic, event-driven mechanism enables the targeting of historically "undruggable" proteomes and circumvents acquired resistance. However, the field faces formidable challenges, including suboptimal pharmacokinetic profiles, the stoichiometric "hook effect," and a disproportionate reliance on a limited pool of E3 ligases (notably cereblon (CRBN) and von Hippel-Lindau (VHL)). This review critically examines PROTAC core principles and provides a nuanced functional categorization across oncology, immune modulation, neurodegenerative diseases, and basic research. We further evaluate three pivotal technical strategies-degrader architecture innovations, conditional activation modalities, and advanced delivery platforms-while systematically appraising current clinical progress. Finally, we discuss key limitations and future translational directions, aiming to provide a realistic roadmap for the next-generation of TPD therapeutics.
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Registered trials
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