Evidence map›Paper›PMID 35042023›Full record

ReviewCurrent opinion in chemical biology2022

Targeted protein degradation: Emerging concepts and protein state-specific targeting principles.

Andrew J Tao, Gillian E Gadbois, Stanley A Buczynski, Fleur M Ferguson

Abstract readReview
In one paragraph

Review in Current opinion in chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
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

4 authors.

Andrew J TaoDepartment of Chemistry & Biochemistry, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
Gillian E GadboisDepartment of Chemistry & Biochemistry, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
Stanley A BuczynskiDepartment of Chemistry & Biochemistry, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
Fleur M FergusonDepartment of Chemistry & Biochemistry, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA. Electronic address: fmferguson@ucsd.edu.

Funding

Molecular Biophysics Training Grant at UC San DiegoT32GM139795 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Galia Debelouchina, ELIZABETH A. KOMIVES · 2021 to 2026
$3.0M
NIGMS NIH HHS T32 GM139795
6 · The paper itself

Abstract

Targeted protein degraders are heterobifunctional small molecules that link a target ligand or bait to an E3-ligase binder via a chemical spacer. Upon entering the cell, these ligands trigger the formation of a ternary complex between the target protein, degrader and E3-ligase, which leads to target polyubiquitination and proteasomal degradation. In recent years, TPD has expanded rapidly as a field, becoming the modality of choice in drug discovery and chemical probe development. This has been driven by the unique pharmacology of these molecules, which allows for fast and reversible knockdown of the target protein. Recent studies have demonstrated that degraders with specificity for a defined subpopulation of a protein-of-interest can be developed, giving rise to the emerging concept of protein state-specific targeting. In this article, we review advances towards developing degraders that differentiate between target protein subpopulations based on their; activation state, oligomerization state, cellular localization state, and cell type.

Indexed as

ProteinsProteolysisUbiquitin-Protein LigasesLigandsUbiquitinationLigandsProteinsUbiquitin-Protein LigasesDegradersMolecular gluesPROTACsTargeted protein degradation

Identifiers

PMID35042023
PMCPMC9701552

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Registered trials

None linked

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.