{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["16(1)"],"submitter":["Nalawansha DA"],"pubmed_abstract":["Proximity-inducing modalities that co-opt cellular pathways offer new opportunities to regulate oncogenic drivers. Inspired by the success of proximity-based chimeras in both intracellular and extracellular target space, here we describe the development of LYsosome Membrane TArgeting Chimeras (LYMTACs) as a small molecule-based platform that functions intracellularly to modulate the membrane proteome. Conceptually, LYMTACs are heterobifunctional small molecules that co-opt short-lived lysosomal membrane proteins (LMPs) as effectors to deliver targets for lysosomal degradation. We demonstrate that a promiscuous kinase inhibitor-based LYMTAC selectively targets membrane proteins for lysosomal degradation via RNF152, a short-lived LMP. We extend this concept by showing that oncogenic KRASG12D"],"journal":["Nature communications"],"pagination":["7812"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12370906"],"repository":["biostudies-literature"],"pubmed_title":["LYMTACs:chimeric small molecules repurpose lysosomal membrane proteins for target protein relocalization and degradation."],"pmcid":["PMC12370906"],"pubmed_authors":["Lanman BA","Husemoen G","Sadhukhan A","Guenette RG","Kapoor R","De Sousa E Melo F","Nalawansha DA","Archunan S","Koirala S","Li S","Tran AT","Wilde C","Potts PR","Xie J","Smith CE","Mazis G","Agnihotram MK","Ashton KS","Wurz RP","Deng W"],"additional_accession":[]},"is_claimable":false,"name":"LYMTACs:chimeric small molecules repurpose lysosomal membrane proteins for target protein relocalization and degradation.","description":"Proximity-inducing modalities that co-opt cellular pathways offer new opportunities to regulate oncogenic drivers. Inspired by the success of proximity-based chimeras in both intracellular and extracellular target space, here we describe the development of LYsosome Membrane TArgeting Chimeras (LYMTACs) as a small molecule-based platform that functions intracellularly to modulate the membrane proteome. Conceptually, LYMTACs are heterobifunctional small molecules that co-opt short-lived lysosomal membrane proteins (LMPs) as effectors to deliver targets for lysosomal degradation. We demonstrate that a promiscuous kinase inhibitor-based LYMTAC selectively targets membrane proteins for lysosomal degradation via RNF152, a short-lived LMP. We extend this concept by showing that oncogenic KRASG12D","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-08T10:44:06.509Z","creation":"2026-04-07T23:47:02.296Z"},"accession":"S-EPMC12370906","cross_references":{"pubmed":["40841368"],"doi":["10.1038/s41467-025-63128-4"]}}