ArticleCell discovery2024
Pharmacology of LRRK2 with type I and II kinase inhibitors revealed by cryo-EM.
Article in Cell discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
What it found
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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.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Article
- Diffusion-Based Generative Model With Scaffold-Hopping Strategy Yields Highly Potent Bioactive Molecules.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- An LRRK2 variant blocks NCOA4 trafficking upon iron overload, leading to ferroptotic death.Journal of cell science · 2026Article
- The structural basis for LRRK2's activation and autoinhibition.bioRxiv : the preprint server for biology · 2026Article
- Proximity proteomics reveals a co-evolved LRRK2-regulatory network linked to centrosomes.EMBO reports · 2026Article
- Elucidating the molecular interplay between LRRK2 and Rab GTPases.bioRxiv : the preprint server for biology · 2026Article
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Discovery of Novel Chemotype LRRK2 Inhibitors Through AlphaFold2-Generated Structure-Based Docking Screen.International journal of molecular sciences · 2026Article
- Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026Review
- Discovery of multitargeting single agents as a novel route to the potential treatment of neurodegenerative diseases.Bioorganic & medicinal chemistry letters · 2026Article
- Selective Stabilization of LRRK2 Kinase Conformations Reveals Distinct Modes of Action for Type I and II Inhibitors.Cell biochemistry and biophysics · 2026Article
- The genetic architecture of Parkinson's disease on the Island of Crete.NPJ Parkinson's disease · 2025Article
- Enhancing kinase-inhibitor activity and selectivity prediction through contrastive learning.Nature communications · 2025Article
- Structural basis for MEKK2 dimerization and substrate recognition.Nature communications · 2025Article
- Article
- Comparative Molecular Dynamics Reveals How LRRK2 Inhibitors Distinguish G2019S from Wild-Type.Neurochemical research · 2025Article
- Structural biology of Parkinson's disease-associated leucine-rich repeat kinase 2 (LRRK2).The Journal of biological chemistry · 2025Review
- Cryo-electron tomography reveals the microtubule-bound form of inactive LRRK2.bioRxiv : the preprint server for biology · 2025Article
- Type II kinase inhibitors that target Parkinson's disease-associated LRRK2.Science advances · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
LRRK2 is one of the most promising drug targets for Parkinson's disease. Though type I kinase inhibitors of LRRK2 are under clinical trials, alternative strategies like type II inhibitors are being actively pursued due to the potential undesired effects of type I inhibitors. Currently, a robust method for LRRK2-inhibitor structure determination to guide structure-based drug discovery is lacking, and inhibition mechanisms of available compounds are also unclear. Here we present near-atomic-resolution structures of LRRK2 with type I (LRRK2-IN-1 and GNE-7915) and type II (rebastinib, ponatinib, and GZD-824) inhibitors, uncovering the structural basis of LRRK2 inhibition and conformational plasticity of the kinase domain with molecular dynamics (MD) simulations. Type I and II inhibitors bind to LRRK2 in active-like and inactive conformations, so LRRK2-inhibitor complexes further reveal general structural features associated with LRRK2 activation. Our study provides atomic details of LRRK2-inhibitor interactions and a framework for understanding LRRK2 activation and for rational drug design.
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.