Evidence map›Paper›PMID 31666732›Full record

ArticleNature reviews. Drug discovery2019

Targeted protein degradation: expanding the toolbox.

Matthieu Schapira, Matthew F Calabrese, Alex N Bullock, Craig M Crews

Abstract read
PubMed Publisher
In one paragraph

Article in Nature reviews. Drug discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 467 papers.

0numbers the graph read from it
0cells of the map it votes in
467citing papers in PubMed
35.8field-weighted citation impact, top 1% of its field
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

467 citing papers in PubMed, 894 citations in OpenAlex.

  1. PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026
    Review
  2. Evolving CRBN ligands enhance the drug-like properties of protein degraders.Journal of enzyme inhibition and medicinal chemistry · 2026
    Review
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  13. Integrated OAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Tricarbonyl Rhenium-Based PROTACs Degrade the SARS-CoV-2 Mpro Protease.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026
    Article
  19. Article
  20. Review

407 more citing papers are in PubMed but not listed here.

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 at 4 institutions in 3 countries.

Matthieu SchapiraStructural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada. matthieu.schapira@utoronto.ca.ORCID http://orcid.org/0000-0002-1047-3309
Matthew F CalabreseDiscovery Sciences, Pfizer Worldwide Research and Development, Groton, CT, USA.
Alex N BullockStructural Genomics Consortium, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-6757-0436
Craig M CrewsDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-8456-2005
Pfizer (United States) · USUniversity of Oxford · GBUniversity of Toronto · CAYale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proteolysis-targeting chimeras (PROTACs) and related molecules that induce targeted protein degradation by the ubiquitin-proteasome system represent a new therapeutic modality and are the focus of great interest, owing to potential advantages over traditional occupancy-based inhibitors with respect to dosing, side effects, drug resistance and modulating 'undruggable' targets. However, the technology is still maturing, and the design elements for successful PROTAC-based drugs are currently being elucidated. Importantly, fewer than 10 of the more than 600 E3 ubiquitin ligases have so far been exploited for targeted protein degradation, and expansion of knowledge in this area is a key opportunity. Here, we briefly discuss lessons learned about targeted protein degradation in chemical biology and drug discovery and systematically review the expression profile, domain architecture and chemical tractability of human E3 ligases that could expand the toolbox for PROTAC discovery.

Indexed as

Molecular Targeted TherapyEnzyme InhibitorsHumansNeoplasmsProteolysisUbiquitin-Protein LigasesEnzyme InhibitorsUbiquitin-Protein Ligases

Identifiers

PMID31666732
OpenAlexW2982554531

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.