Evidence map›Paper›PMID 41290730›Full record

ArticleScientific reports2025

Discovery of a Proteolysis Targeting Chimera for TRKA and RET-derived oncoproteins.

Marialuisa Moccia, Lingzhi Zhang, Zhengyu Wang, Minmin Wang, Giorgia Federico, Massimo Santoro, Hong-Yu Li, Francesca Carlomagno

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Marialuisa Moccia *Istituto degli Endotipi in Oncologia, Metabolismo e Immunologia "G. Salvatore" (IEOMI) del CNR, Naples, Italia.
Lingzhi Zhang *Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Naples, Italia.
Zhengyu Wang *Department of Pharmacology, University of Texas Health San Antonio, San Antonio, TX, USA.
Minmin WangDepartment of Pharmacology, University of Texas Health San Antonio, San Antonio, TX, USA.
Giorgia FedericoDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Naples, Italia.
Massimo SantoroDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Naples, Italia.
Hong-Yu LiDepartment of Pharmacology, University of Texas Health San Antonio, San Antonio, TX, USA. lih1@uthscsa.edu.
Francesca CarlomagnoDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Naples, Italia. francesca.carlomagno@unina.it.

Funding

Fondazione AIRC per la ricerca sul cancro ETS IG20793Ministero dell'Università e della Ricerca PRIN 2022ELYS5F
6 · The paper itself

Abstract

We designed Proteolysis Targeting Chimeras (PROTACs) to target Tropomyosin Receptor Kinase A (TRKA) and Rearranged during Transfection (RET) oncogenic proteins. We analyzed a series of 22 PROTACs, based on the RET and TRKA small molecule inhibitor Pz-1 and ligands of E3 ligase complex component Cereblon (CRBN). The compounds were tested in TPC-1 and KM12 cells, derived from papillary thyroid carcinoma and colorectal carcinoma, and harboring the CCDC6-RET and TPM3-TRKA oncoproteins, respectively. We identified several RET and TPM3-TRKA PROTACs, able to induce their degradation. Consistently, one of the most active degraders, compound 9, exhibited a strong anti-proliferative effect in several cancer cell lines derived from human medullary and papillary thyroid, lung and colon cancers, displaying either RET or TRKA-derived oncoproteins, with an IC

Indexed as

Antineoplastic AgentsOncogene Proteins, FusionProteolysisProto-Oncogene Proteins c-retReceptor, trkAAdaptor Proteins, Signal TransducingAnimalsCell Line, TumorCell ProliferationHumansMiceProteasome Endopeptidase ComplexProtein Kinase InhibitorsProteolysis Targeting ChimeraUbiquitinationUbiquitin-Protein LigasesAdaptor Proteins, Signal TransducingAntineoplastic AgentsCRBN protein, humanNTRK1 protein, humanOncogene Proteins, FusionProteasome Endopeptidase ComplexProtein Kinase InhibitorsProteolysis Targeting ChimeraProto-Oncogene Proteins c-retReceptor, trkARET protein, humanUbiquitin-Protein Ligases

Identifiers

PMID41290730
PMCPMC12647785

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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.