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Covalent Recruitment of NEDD4 for Targeted Protein Degradation: Rational Design of Small Molecular Degraders

Covalent Modifiers

2025 , 147 , 25 , 21512–21525 [link] Targeted protein degradation (TPD) has emerged as a promising therapeutic strategy for treating various diseases. However, current small molecule degraders predominantly rely on a limited set of E3 ubiquitin ligases, such as CRBN and VHL, which restricts their applications.

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Rational Design of CDK12/13 and BRD4 Molecular Glue Degraders

Covalent Modifiers

link] Targeted protein degradation (TPD) is an emerging therapeutic approach for the selective elimination of disease-related proteins. While molecular glue degraders exhibit drug-like properties, their discovery has traditionally been serendipitous and often requires post-hoc rationalization.

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Bristol Myers Squibb Highlights Targeted Protein Degradation Data, Including CELMoD Agents, at EHA 2025

The Pharma Data

Expanding Targeted Protein Degradation in Hematologic Malignancies Targeted protein degradation is a powerful therapeutic approach designed to destroy disease-driving proteins within cells, thereby inhibiting their ability to contribute to disease progression.

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Protein degraders: chasing undruggable targets

BioPharma Drive: Drug Pricing

Love Employee via Getty Images For decades now, scientists have been experimenting with a new way to target and destroy proteins linked to disease. Unlike most approved drugs, which work by turning cell signaling up or down like a dimmer switch, this approach aims to rid cells of problem proteins entirely.

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Scientists generate new targeted protein degradation system that tunes a cell’s own proteins

Broad Institute

In one approach, they mark targeted proteins with “destroy me” tags that work with small molecules known as molecular glues to prompt the cell’s own protein-clearing machinery to gobble up the proteins. Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.

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Targeted protein degradation: turning undruggable targets into druggable targets

Drug Target Review

TPD is a rapidly evolving therapeutic modality to degrade a disease-causing proteins, thereby eliminating their function specifically. 1 TPD is expected to challenge undruggable proteins, which are highly difficult to target by conventional small molecules. How does TPD work?

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Women in STEM with Juliet Williams

Drug Target Review

Shortly after finishing my studies, I landed my first job in industry working on cell biology research for several disease indications. TPD engages the body’s natural protein recycling system by selectively eliminating disease-causing proteins, ultimately addressing the root cause of disease.