ArticleBioorganic & medicinal chemistry letters2023
Development of a highly potent and selective degrader of LRRK2.
Article in Bioorganic & medicinal chemistry letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Pathological Protein Targets in Parkinson's Disease: Progress Towards the Development of Disease-Modifying Therapies.CNS drugs · 2026Review
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- Active Learning-Guided Hit Optimization for the Leucine-Rich Repeat Kinase 2 WDR Domain Based on In Silico Ligand-Binding Affinities.Journal of chemical information and modeling · 2025Article
- Leucine-rich repeat kinase 2 biomarkers for Parkinson's disease.The Biochemical journal · 2025Review
- Advancements in PROTAC-based therapies for neurodegenerative diseases.Future medicinal chemistry · 2025Review
- CACHE Challenge #1: Docking with GNINA Is All You Need.Journal of chemical information and modeling · 2024Article
- LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting.Trends in molecular medicine · 2024Review
- A designed ankyrin-repeat protein that targets Parkinson's disease-associated LRRK2.The Journal of biological chemistry · 2024Article
- Drug Development for Alzheimer's and Parkinson's Disease: Where Do We Go Now?Pharmaceutics · 2024Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
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 selectivity for LRKK2 when assessed in a of 468 panel kinases and serves the dual purpose of eliminating both the kinase activity as well as the scaffolding function of LRRK2.
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What OpenQuestion holds
Registered trials
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.