{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hatcher JM"],"funding":["Michael J Fox Foundation for Parkinson's Research","GlaxoSmithKline","Medical Research Council","Merck KGaA","NCI NIH HHS"],"pagination":["129449"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11837620"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["94"],"pubmed_abstract":["The discovery of disease-modifying therapies for Parkinson's Disease (PD) represents a critical need in neurodegenerative medicine. Genetic mutations in leucine-rich repeat kinase 2 (LRRK2) are risk factors for the development of PD, and some of these mutations have been linked to increased LRRK2 kinase activity and neuronal toxicity in cellular and animal models. Furthermore, LRRK2 function as a scaffolding protein in several pathways has been implicated as a plausible mechanism underlying neurodegeneration caused by LRRK2 mutations. Given that both the kinase activity and scaffolding function of LRRK2 have been linked to neurodegeneration, we developed proteolysis-targeting chimeras (PROTACs) targeting LRRK2. The degrader molecule JH-XII-03-02 (6) displayed high potency and remarkable se"],"journal":["Bioorganic & medicinal chemistry letters"],"pubmed_title":["Development of a highly potent and selective degrader of LRRK2."],"pmcid":["PMC11837620"],"funding_grant_id":["R01 CA218278","MJFF-005430","MC_UU_00018/1","MC_UU_12016/2"],"pubmed_authors":["Davies P","Gray NS","Hatcher JM","Vatsan PS","Sarhan AR","Alessi DR","Zwirek M","Tonelli F"],"additional_accession":[]},"is_claimable":false,"name":"Development of a highly potent and selective degrader of LRRK2.","description":"The discovery of disease-modifying therapies for Parkinson's Disease (PD) represents a critical need in neurodegenerative medicine. Genetic mutations in leucine-rich repeat kinase 2 (LRRK2) are risk factors for the development of PD, and some of these mutations have been linked to increased LRRK2 kinase activity and neuronal toxicity in cellular and animal models. Furthermore, LRRK2 function as a scaffolding protein in several pathways has been implicated as a plausible mechanism underlying neurodegeneration caused by LRRK2 mutations. Given that both the kinase activity and scaffolding function of LRRK2 have been linked to neurodegeneration, we developed proteolysis-targeting chimeras (PROTACs) targeting LRRK2. The degrader molecule JH-XII-03-02 (6) displayed high potency and remarkable se","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Oct","modification":"2025-04-26T12:28:31.899Z","creation":"2025-04-26T12:28:31.899Z"},"accession":"S-EPMC11837620","cross_references":{"pubmed":["37591317"],"doi":["10.1016/j.bmcl.2023.129449"]}}