ArticleChemistry & biology2012
Rational design of small molecule inhibitors targeting the Rac GTPase-p67(phox) signaling axis in inflammation.
Article in Chemistry & biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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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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
27 citing papers in PubMed, 60 citations in OpenAlex.
- Role of NADPH oxidase 2-derived reactive oxygen species in cardiac electrophysiological disorders.Channels (Austin, Tex.) · 2026Review
- Cardiomyocyte Rac1 signaling in hypertrophy, arrhythmia, and cardiac stress adaptation.Journal of molecular and cellular cardiology plus · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors.Journal of medicinal chemistry · 2023Review
- Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies.Antioxidants (Basel, Switzerland) · 2023Review
- NADPH oxidase family proteins: signaling dynamics to disease management.Cellular & molecular immunology · 2022Review
- RAC1 Activation as a Potential Therapeutic Option in Metastatic Cutaneous Melanoma.Biomolecules · 2021Review
- Modeling Virus-Induced Inflammation in Zebrafish: A Balance Between Infection Control and Excessive Inflammation.Frontiers in immunology · 2021Review
- Small molecule targeting the Rac1-NOX2 interaction prevents collagen-related peptide and thrombin-induced reactive oxygen species generation and platelet activation.Journal of thrombosis and haemostasis : JTH · 2018Article
- Inhibition of Rac family protein impairs colitis and colitis-associated cancer in mice.American journal of cancer research · 2018Article
- The novel NADPH oxidase 4 selective inhibitor GLX7013114 counteracts human islet cell death in vitro.PloS one · 2018Article
- Tumor suppressor NPRL2 induces ROS production and DNA damage response.Scientific reports · 2017Article
- Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms.Small GTPases · 2017Review
- Rho GTPases: Anti- or pro-neoplastic targets?Oncogene · 2017Review
- Rac Attack: Modulation of the Small GTPase Rac in Inflammatory Bowel Disease and Thiopurine Therapy.Molecular diagnosis & therapy · 2016Review
- NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress.Antioxidants & redox signaling · 2015Review
- Approaches of targeting Rho GTPases in cancer drug discovery.Expert opinion on drug discovery · 2015Review
- Rational design of small molecule inhibitors targeting the Ras GEF, SOS1.Chemistry & biology · 2014Article
- The quest for selective nox inhibitors and therapeutics: challenges, triumphs and pitfalls.Antioxidants & redox signaling · 2014Review
- Potent hepatitis C inhibitors bind directly to NS5A and reduce its affinity for RNA.Scientific reports · 2014Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The NADPH oxidase enzyme complex, NOX2, is responsible for reactive oxygen species production in neutrophils and has been recognized as a key mediator of inflammation. Here, we have performed rational design and in silico screen to identify a small molecule inhibitor, Phox-I1, targeting the interactive site of p67(phox) with Rac GTPase, which is a necessary step of the signaling leading to NOX2 activation. Phox-I1 binds to p67(phox) with a submicromolar affinity and abrogates Rac1 binding and is effective in inhibiting NOX2-mediated superoxide production dose-dependently in human and murine neutrophils without detectable toxicity. Medicinal chemistry characterizations have yielded promising analogs and initial information of the structure-activity relationship of Phox-I1. Our studies suggest the potential utility of Phox-I class inhibitors in NOX2 oxidase inhibition and present an application of rational targeting of a small GTPase-effector interface.
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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.