{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Moccia M"],"funding":["Ministero dell'Università e della Ricerca","Fondazione AIRC per la ricerca sul cancro ETS"],"pagination":["41770"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12647785"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_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, displa"],"journal":["Scientific reports"],"pubmed_title":["Discovery of a Proteolysis Targeting Chimera for TRKA and RET-derived oncoproteins."],"pmcid":["PMC12647785"],"funding_grant_id":["IG20793","PRIN 2022ELYS5F"],"pubmed_authors":["Wang M","Federico G","Moccia M","Santoro M","Zhang L","Li HY","Carlomagno F","Wang Z"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of a Proteolysis Targeting Chimera for TRKA and RET-derived oncoproteins.","description":"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, displa","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T19:53:46.483Z","creation":"2026-05-21T03:11:36.429Z"},"accession":"S-EPMC12647785","cross_references":{"pubmed":["41290730"],"doi":["10.1038/s41598-025-25687-w"]}}