ArticleBritish journal of pharmacology2013
Characterization of AQX-1125, a small-molecule SHIP1 activator: Part 2. Efficacy studies in allergic and pulmonary inflammation models 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, 50 citations in OpenAlex.
- Systemic immune programming in the life course of childhood asthma: a new perspective on monocyte pre-activation and trained immunity.Frontiers in immunology · 2026Review
- Promising Experimental Treatment in Animal Models and Human Studies of Interstitial Cystitis/Bladder Pain Syndrome.International journal of molecular sciences · 2024Review
- Herpes simplex keratitis: A brief clinical overview.World journal of virology · 2024Review
- Progression of Acute Lung Injury in Intratracheal LPS Rat Model: Efficacy of Fluticasone, Dexamethasone, and Pirfenidone.Pharmacology · 2024Article
- Structure-Activity Studies on Bis-Sulfonamide SHIP1 Activators.Molecules (Basel, Switzerland) · 2023Article
- Synthetic studies on the indane SHIP1 agonist AQX-1125.Organic & biomolecular chemistry · 2022Article
- SHIP1 Activator AQX-1125 Regulates Osteogenesis and Osteoclastogenesis Through PI3K/Akt and NF-κb Signaling.Frontiers in cell and developmental biology · 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
- Targeting SHIP-1 in Myeloid Cells Enhances Trained Immunity and Boosts Response to Infection.Cell reports · 2018Article
- 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
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe efficacy of AQX-1125, a small-molecule SH2-containing inositol-5'-phosphatase 1 (SHIP1) activator and clinical development candidate, is investigated in rodent models of inflammation. EXPERIMENTAL APPROACH: AQX-1125 was administered orally in a mouse model of passive cutaneous anaphylaxis (PCA) and a number of rodent models of respiratory inflammation including: cigarette smoke, LPS and ovalbumin (OVA)-mediated airway inflammation. SHIP1 dependency of the AQX-1125 mechanism of action was investigated by comparing the efficacy in wild-type and SHIP1-deficient mice subjected to an intrapulmonary LPS challenge.
resultsAQX-1125 exerted anti-inflammatory effects in all of the models studied. AQX-1125 decreased the PCA response at all doses tested. Using bronchoalveolar lavage (BAL) cell counts as an end point, oral or aerosolized AQX-1125 dose dependently decreased the LPS-mediated pulmonary neutrophilic infiltration at 3-30 mg kg⁻¹ and 0.15-15 μg kg⁻¹ respectively. AQX-1125 suppressed the OVA-mediated airway inflammation at 0.1-10 mg kg⁻¹. In the smoke-induced airway inflammation model, AQX-1125 was tested at 30 mg kg⁻¹ and significantly reduced the neutrophil infiltration of the BAL fluid. AQX-1125 (10 mg kg⁻¹) decreased LPS-induced pulmonary neutrophilia in wild-type mice but not in SHIP1-deficient mice.
conclusionsThe SHIP1 activator, AQX-1125, suppresses leukocyte accumulation and inflammatory mediator release in rodent models of pulmonary inflammation and allergy. As shown in the mouse model of LPS-induced lung inflammation, the efficacy of the compound is dependent on the presence of SHIP1. Pharmacological SHIP1 activation may have clinical potential for the treatment of pulmonary inflammatory diseases.
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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.