ArticleACS chemical biology2011
Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson's disease-related toxicity in human neurons.
Article in ACS chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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.
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.
Who cites it
65 citing papers in PubMed, 149 citations in OpenAlex.
- CZC54252 overcomes Osimertinib resistance by targeting EGFRBMC pharmacology & toxicology · 2026Article
- MPMB-DR: Meta-path Integration of Multi-source Biological Information for Drug Repositioning.Interdisciplinary sciences, computational life sciences · 2026Article
- Article
- Type II kinase inhibitors that target Parkinson's disease-associated LRRK2.Science advances · 2025Article
- Exploring LRRK2-dependent Mechanisms in Parkinson's Disease Therapy.CNS & neurological disorders drug targets · 2025Review
- The design and development of LRRK2 inhibitors as novel therapeutics for Parkinson's disease.Future medicinal chemistry · 2025Review
- Development of BODIPY FL SNS 032 as a Versatile Probe for Constitutive Androstane Receptor and Multiple Kinases.ACS medicinal chemistry letters · 2024Article
- Article
- Efficacy of a benzothiazole-based LRRK2 inhibitor in oligodendrocyte precursor cells and in a murine model of multiple sclerosis.CNS neuroscience & therapeutics · 2024Article
- Article
- Characterization of 2,4-Dianilinopyrimidines Against FiveACS medicinal chemistry letters · 2023Article
- Identification of a chemical probe for lipid kinase phosphatidylinositol-5-phosphate 4-kinase gamma (PI5P4Kγ).Current research in chemical biology · 2023Article
- Emerging targets signaling for inflammation in Parkinson's disease drug discovery.Metabolic brain disease · 2022Review
- Structural Insights and Development of LRRK2 Inhibitors for Parkinson's Disease in the Last Decade.Genes · 2022Review
- Development of a physiologically relevant and easily scalable LUHMES cell-based model of G2019S LRRK2-driven Parkinson's disease.Disease models & mechanisms · 2021Article
- Review
- Pathogenic LRRK2 requires secondary factors to induce cellular toxicity.Bioscience reports · 2020Article
- Defects in mRNA Translation in LRRK2-Mutant hiPSC-Derived Dopaminergic Neurons Lead to Dysregulated Calcium Homeostasis.Cell stem cell · 2020Article
- Dopaminergic neurodegeneration induced by Parkinson's disease-linked G2019S LRRK2 is dependent on kinase and GTPase activity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Future of Targeted Gene-Based Treatment Strategies and Biomarkers in Parkinson's Disease.Biomolecules · 2020Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Leucine-rich repeat kinase-2 (LRRK2) mutations are the most important cause of familial Parkinson's disease, and non-selective inhibitors are protective in rodent disease models. Because of their poor potency and selectivity, the neuroprotective mechanism of these tool compounds has remained elusive so far, and it is still unknown whether selective LRRK2 inhibition can attenuate mutant LRRK2-dependent toxicity in human neurons. Here, we employ a chemoproteomics strategy to identify potent, selective, and metabolically stable LRRK2 inhibitors. We demonstrate that CZC-25146 prevents mutant LRRK2-induced injury of cultured rodent and human neurons with mid-nanomolar potency. These precise chemical probes further validate this emerging therapeutic strategy. They will enable more detailed studies of LRRK2-dependent signaling and pathogenesis and accelerate drug discovery.
Indexed as
Identifiers
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.