Evidence map›Paper›PMID 41381043›Full record

ArticleJournal of medicinal chemistry2025

Leveraging Targeted Protein Degradation for G Protein-Coupled Receptors: The Development of CCR2 Molecular Degraders.

Khaled Essa, Natalia V Ortiz Zacarías, Sascha Roth, Bo-Tao Xin, Sabine de Winter, Cas van der Horst, Bente Bleijs, Richard A de Heiden, Rodanthi Voulgaraki, Elsa Neubert and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

16 authors.

Khaled EssaDivision of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden 2333 CC, The Netherlands.
Natalia V Ortiz ZacaríasDivision of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden 2333 CC, The Netherlands.
Sascha RothSafety Innovation and PROTAC Safety, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge CB2 0SL, United Kingdom.
Bo-Tao XinDepartment of Cell and Chemical Biology, Chemical Immunology, Leiden University Medical Centre, Leiden 2333 ZC, The Netherlands.
Sabine de WinterDivision of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden 2333 CC, The Netherlands.ORCID 0009-0002-1152-7994
Cas van der HorstDivision of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden 2333 CC, The Netherlands.
Bente BleijsDivision of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden 2333 CC, The Netherlands.
Richard A de HeidenDivision of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden 2333 CC, The Netherlands.
Rodanthi VoulgarakiDivision of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden 2333 CC, The Netherlands.
Elsa NeubertDivision of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden 2333 CC, The Netherlands.ORCID 0000-0003-4642-9112
Huib OvaaDepartment of Cell and Chemical Biology, Chemical Immunology, Leiden University Medical Centre, Leiden 2333 ZC, The Netherlands.
Erik H J DanenDivision of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden 2333 CC, The Netherlands.
Monique P C MulderDepartment of Cell and Chemical Biology, Chemical Immunology, Leiden University Medical Centre, Leiden 2333 ZC, The Netherlands.ORCID 0000-0001-5386-7132
Kevin MoreauSafety Innovation and PROTAC Safety, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge CB2 0SL, United Kingdom.ORCID 0000-0002-3688-3998
Daan van der EsDivision of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden 2333 CC, The Netherlands.ORCID 0000-0003-3662-8177
Laura H HeitmanDivision of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden 2333 CC, The Netherlands.ORCID 0000-0002-1381-8464

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Targeted protein degradation (TPD) is one of the most prominent and rapidly advancing modalities in drug discovery. However, only few degraders have been reported for the membrane-bound G protein-coupled receptors (GPCRs). Therefore, using CC chemokine receptor 2 (CCR2) as a GPCR model, we synthesized potential CCR2 molecular degraders. The putative proteolysis-targeting chimeras (PROTACs) employed an allosteric intracellular CCR2 ligand tethered to commonly used E3 ligase ligands. Among these compounds, LUF7996 (

Indexed as

ProteolysisReceptors, CCR2Receptors, G-Protein-CoupledCell MovementHEK293 CellsHumansLigandsMonocytesUbiquitin-Protein LigasesCCR2 protein, humanLigandsReceptors, CCR2Receptors, G-Protein-CoupledUbiquitin-Protein Ligases

Identifiers

PMID41381043
PMCPMC12750996

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.