ArticleJournal of medicinal chemistry2014
Discovery of 2-[5-(4-Fluorophenylcarbamoyl)pyridin-2-ylsulfanylmethyl]phenylboronic Acid (SX-517): Noncompetitive Boronic Acid Antagonist of CXCR1 and CXCR2.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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
13 citing papers in PubMed, 38 citations in OpenAlex.
- Boron-containing anticancer agents: a target-centric review of structure-activity relationships and clinical pipeline.Archives of pharmacal research · 2025Review
- Targeting CXCR2 signaling in inflammatory lung diseases: neutrophil-driven inflammation and emerging therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Comprehensive profiling of chemokine and NETosis-associated genes in sarcopenia: construction of a machine learning-based diagnostic nomogram.Frontiers in medicine · 2025Article
- Review
- Therapeutic inhibition of CXCR1/2: where do we stand?Internal and emergency medicine · 2023Review
- CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth.Molecular cancer · 2023Article
- The Boron Advantage: The Evolution and Diversification of Boron's Applications in Medicinal Chemistry.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Discovery of 1,5-Dihydro-4ACS medicinal chemistry letters · 2021Article
- Tumor Plasticity and Resistance to Immunotherapy.Trends in cancer · 2020Review
- Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases.Theranostics · 2017Review
- Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders.ACS medicinal chemistry letters · 2016Article
- Boronic acid-containing aminopyridine- and aminopyrimidinecarboxamide CXCR1/2 antagonists: Optimization of aqueous solubility and oral bioavailability.Bioorganic & medicinal chemistry letters · 2015Article
- Boronic acid-containing CXCR1/2 antagonists: Optimization of metabolic stability, in vivo evaluation, and a proposed receptor binding model.Bioorganic & medicinal chemistry letters · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
The G protein-coupled chemokine receptors CXCR1 and CXCR2 play key roles in inflammatory diseases and carcinogenesis. In inflammation, they activate and recruit polymorphonuclear cells (PMNs) through binding of the chemokines CXCL1 (CXCR1) and CXCL8 (CXCR1 and CXCR2). Structure-activity studies that examined the effect of a novel series of S-substituted 6-mercapto-N-phenyl-nicotinamides on CXCL1-stimulated Ca(2+) flux in whole human PMNs led to the discovery of 2-[5-(4-fluorophenylcarbamoyl)pyridin-2-ylsulfanylmethyl]phenylboronic acid (SX-517), a potent noncompetitive boronic acid CXCR1/2 antagonist. SX-517 inhibited CXCL1-induced Ca(2+) flux (IC50 = 38 nM) in human PMNs but had no effect on the Ca(2+) flux induced by C5a, fMLF, or PAF. In recombinant HEK293 cells that stably expressed CXCR2, SX-517 antagonized CXCL8-induced [(35)S]GTPγS binding (IC50 = 60 nM) and ERK1/2 phosphorylation. Inhibition was noncompetitive, with SX-517 unable to compete the binding of [(125)I]-CXCL8 to CXCR2 membranes. SX-517 (0.2 mg/kg iv) significantly inhibited inflammation in an in vivo murine model. SX-517 is the first reported boronic acid chemokine antagonist and represents a novel pharmacophore for CXCR1/2 antagonism.
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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.