ArticleBritish journal of pharmacology2013
Characterization of AQX-1125, a small-molecule SHIP1 activator: Part 1. Effects on inflammatory cell activation and chemotaxis in vitro and pharmacokinetic characterization in vivo.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 63 citations in OpenAlex.
- Neutrophil heterogeneity and plasticity: unveiling the multifaceted roles in health and disease.MedComm · 2025Review
- Promising Experimental Treatment in Animal Models and Human Studies of Interstitial Cystitis/Bladder Pain Syndrome.International journal of molecular sciences · 2024Review
- The Functional Roles of the Src Homology 2 Domain-Containing Inositol 5-Phosphatases SHIP1 and SHIP2 in the Pathogenesis of Human Diseases.International journal of molecular sciences · 2024Review
- Regulation of inositol 5-phosphatase activity by the C2 domain of SHIP1 and SHIP2.Structure (London, England : 1993) · 2024Article
- Structure-Activity Studies on Bis-Sulfonamide SHIP1 Activators.Molecules (Basel, Switzerland) · 2023Article
- Article
- A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours.Frontiers in pharmacology · 2023Article
- Synthetic studies on the indane SHIP1 agonist AQX-1125.Organic & biomolecular chemistry · 2022Article
- PI3K inhibitors are finally coming of age.Nature reviews. Drug discovery · 2021Review
- Targeting SHIP1 and SHIP2 in Cancer.Cancers · 2021Review
- Interleukin-10 and Small Molecule SHIP1 Allosteric Regulators Trigger Anti-inflammatory Effects through SHIP1/STAT3 Complexes.iScience · 2020Article
- Preclinical Evaluation of a Novel SHIP1 Phosphatase Activator for Inhibition of PI3K Signaling in Malignant B Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Targeting the FcεRI Pathway as a Potential Strategy to Prevent Food-Induced Anaphylaxis.Frontiers in immunology · 2020Review
- Current Pharmacologic Approaches in Painful Bladder Research: An Update.International neurourology journal · 2017Review
- AQX-1125, small molecule SHIP1 activator inhibits bleomycin-induced pulmonary fibrosis.British journal of pharmacology · 2017Article
- Combination of ginsenoside Rb1 and Rd protects the retina against bright light-induced degeneration.Scientific reports · 2017Article
- Signal transduction and chemotaxis in mast cells.European journal of pharmacology · 2016Review
- Molecular control of PtdIns(3,4,5)P3 signaling in neutrophils.EMBO reports · 2015Review
- Discovery and development of small molecule SHIP phosphatase modulators.Medicinal research reviews · 2014Review
- Phosphoinositides: tiny lipids with giant impact on cell regulation.Physiological reviews · 2013Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe SH2-containing inositol-5'-phosphatase 1 (SHIP1) metabolizes PI(3,4,5)P3 to PI(3,4)P2. SHIP1-deficient mice exhibit progressive inflammation. Pharmacological activation of SHIP1 is emerging as a potential therapy for pulmonary inflammatory diseases. Here we characterize the efficacy of AQX-1125, a small-molecule SHIP1 activator currently in clinical development. EXPERIMENTAL APPROACH: The effects of AQX-1125 were tested in several in vitro assays: on enzyme catalytic activity utilizing recombinant human SHIP1, on Akt phosphorylation in SHIP1-proficient and SHIP1-deficient cell lines, on cytokine release in murine splenocytes, on human leukocyte chemotaxis using modified Boyden chambers and on β-hexosaminidase release from murine mast cells. In addition, pharmacokinetic and drug distribution studies were performed in rats and dogs.
resultsAQX-1125 increased the catalytic activity of human recombinant SHIP1, an effect, which was absent after deletion of the C2 region. AQX-1125 inhibited Akt phosphorylation in SHIP1-proficient but not in SHIP1-deficient cells, reduced cytokine production in splenocytes, inhibited the activation of mast cells and inhibited human leukocyte chemotaxis. In vivo, AQX-1125 exhibited >80% oral bioavailability and >5 h terminal half-life.
conclusionsConsistent with the role of SHIP1 in cell activation and chemotaxis, the SHIP1 activator AQX-1125 inhibits Akt phosphorylation, inflammatory mediator production and leukocyte chemotaxis in vitro. The in vitro effects and the pharmacokinetic properties of the compound make it a suitable candidate for in vivo testing in various models of inflammation.
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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.