ArticleBMC neuroscience2015
Targeted inhibition of the Shroom3-Rho kinase protein-protein interaction circumvents Nogo66 to promote axon outgrowth.
Article in BMC neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Design of precision therapeutics for a CKD risk allele by targeting Shroom3-Rock interaction.Nature communications · 2025Article
- Mapping Shroom3 expression across the adult mouse.Gene expression patterns : GEP · 2025Article
- Article
- Shroom3-Rock interaction and profibrotic function: Resolving mechanism of an intronic CKD risk allele.bioRxiv : the preprint server for biology · 2024Article
- Article
- Inhibitors of protein-protein interactions (PPIs): an analysis of scaffold choices and buried surface area.Current opinion in chemical biology · 2018Review
- Scoria: a Python module for manipulating 3D molecular data.Journal of cheminformatics · 2017Article
- Rho kinase regulates neurite outgrowth of hippocampal neurons via calcium dependent cytoskeleton regulation.American journal of translational research · 2017Article
- Structure of the Shroom-Rho Kinase Complex Reveals a Binding Interface with Monomeric Shroom That Regulates Cell Morphology and Stimulates Kinase Activity.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundInhibitory molecules in the adult central nervous system, including NogoA, impede neural repair by blocking axon outgrowth. The actin-myosin regulatory protein Shroom3 directly interacts with Rho kinase and conveys axon outgrowth inhibitory signals from Nogo66, a C-terminal inhibitory domain of NogoA. The purpose of this study was to identify small molecules that block the Shroom3-Rho kinase protein-protein interaction as a means to modulate NogoA signaling and, in the longer term, enhance axon outgrowth during neural repair.
resultsA high throughput screen for inhibitors of the Shroom3-Rho kinase protein-protein interaction identified CCG-17444 (Chem ID: 2816053). CCG-17444 inhibits the Shroom3-Rho kinase interaction in vitro with micromolar potency. This compound acts through an irreversible, covalent mechanism of action, targeting Shroom3 Cys1816 to inhibit the Shroom3-Rho kinase protein-protein interaction. Inhibition of the Shroom3-Rho kinase protein-protein interaction with CCG-17444 counteracts the inhibitory action of Nogo66 and enhances neurite outgrowth.
conclusionsThis study identifies a small molecule inhibitor of the Shroom3-Rho kinase protein-protein interaction that circumvents the inhibitory action of Nogo66 in neurons. Identification of a small molecule compound that blocks the Shroom3-Rho kinase protein-protein interaction provides a first step towards a potential new strategy for enhancing neural repair.
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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.