rosiptor (AQX-1125) / Neoleukin Therap - LARVOL DELTA

SHIP1 agonist rosiptor inhibits platelet activation and thrombosis by modulating cAMP/cGMP and PI3K/PKC pathway. (PubMed, Eur J Pharmacol) - "Rosiptor enhanced cGMP and cAMP-dependent signal transduction and inhibited agonist-induced PI3K/PKC signaling pathway. In conclusion, our study suggests that rosiptor may have a potential therapeutic role in thrombotic diseases with a reduced risk of bleeding complications."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

The Functional Roles of the Src Homology 2 Domain-Containing Inositol 5-Phosphatases SHIP1 and SHIP2 in the Pathogenesis of Human Diseases. (PubMed, Int J Mol Sci) - "The SHIP1-inhibitor 3-α-aminocholestane (3AC), and SHIP1-activators, such as AQX-435 and AQX-1125, and SHIP2-inhibitors, such as K161 and AS1949490, have been developed and partly tested in clinical trials, which indicates the importance of the SHIP-paralogs as possible targets in the therapy of those diseases. The aim of this article is to provide an overview of the current knowledge about the involvement of SHIP proteins in the pathogenesis of cancer and other human diseases and to create awareness that SHIP1 and SHIP2 are more than just tumor suppressors and oncogenes."

Journal • Review • Allergy • Alzheimer's Disease • Cardiovascular • CNS Disorders • Hematological Malignancies • Immunology • Leukemia • Metabolic Disorders • Oncology

SHIP-1 affects herpetic simplex keratitis prognosis by mediating CD4 T lymphocytes migration through PI3K signaling and transcription factor KLF2 in the cornea. (PubMed, Antiviral Res) - "In the present study, we found that the subconjunctival injection of SHIP-1 activator AQX1125 in mouse HSK model alleviated the corneal inflammatory and angiogenic responses, as well as promoted quicker recovery of the cornea, with significantly fewer infiltration of CD4 T lymphocytes. Furthermore, using primary CD4 T lymphocytes, we observed that by modulating PI3K signaling and the expression of transcription factors KLF2 and CCR7, SHIP-1 could significantly influence the migration of lymphocytes toward CCL19 and 21, which are the "exit cues" for cells to emigrate from inflammatory sites. Thus, we propose that the pharmacological SHIP-1 activation represents a new potential therapeutic approach to control HSK lesions, and its function on the CCR7-CCL19/21 biological axis may be a novel underlying mechanism for its anti-inflammatory action."

Journal • Immunology • Inflammation • Keratitis • Ocular Inflammation • Ophthalmology • CCL19 • CCR7 • CD4

Synthetic studies on the indane SHIP1 agonist AQX-1125. (PubMed, Org Biomol Chem) - "The role of the C17 alkene in the biological activity of the system is also investigated, and this functional group is not required for SHIP1 agonist activity. While AQX-1125 shows SHIP1 agonist activity in enzyme assays, it does not show activity in cell based assays similar to other SHIP1 agonists, which limits the utility of this molecule."

Journal • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • Interstitial Cystitis • Musculoskeletal Pain • Pain

SHIP1 Activator AQX-1125 Regulates Osteogenesis and Osteoclastogenesis Through PI3K/Akt and NF-κb Signaling. (PubMed, Front Cell Dev Biol) - "NF-κB signaling was also inhibited through suppression of the phosphorylation of IκBα and P65 induced by RANKL, resulting in diminished osteoclastogenesis. Taken together, our results demonstrate that AQX-1125 may be a promising candidate for preventing and treating bone loss."

Journal • Osteoporosis • Rheumatology • COL1A1 • NFKBIA • PI3K • RELA

CP/CPPS: Efficacy and Safety of AQX-1125 in Subjects With Chronic Prostatitis/Chronic Pelvic Pain Syndrome (clinicaltrials.gov) - P2; N=100; Not yet recruiting; Sponsor: Aquinox Pharmaceuticals (Canada) Inc.

New P2 trial • Biosimilar • CNS Disorders • Immunology • Pain

Aquinox Pharmaceuticals to provide update on secondary endpoints from Phase 2 LEADERSHIP trial in BPS/IC and report second quarter financial results on August 6, 2015 (GlobeNewswire) - "Aquinox Pharmaceuticals...will provide an update on results from secondary endpoints from its recently completed Phase 2 LEADERSHIP randomized clinical trial with AQX-1125 in patients with bladder pain syndrome/interstitial cystitis (BPS/IC). Aquinox will also provide a general business update and report second quarter 2015 financial results on Thursday, August 6th, 2015 after close of U.S. financial markets."

Anticipated P2 data • Pain

Aquinox Pharmaceuticals announces first quarter 2015 financial results (GlobeNewswire) - "Approaching Top Line Data in FLAGSHIP, a Phase 2 clinical trial of AQX-1125 in chronic obstructive pulmonary disease (COPD) exacerbations. Target enrollment in the FLAGSHIP trial was achieved at the end of January 2015. Top-line results are expected near mid-year 2015 with subsequent, secondary analyses expected to be presented at a future scientific meeting."

Anticipated P2 data • Chronic Obstructive Pulmonary Disease

Synthesis and structure activity studies of indene-based SHIP1 agonists (ACS-Sp 2020) - "To facilitate our own studies on the role of SHIP1 in cell signaling, a new synthesis of the SHIP1 agonist AQX-1125 was developed...This sequence utilizes a hydroxy-acid intermediate which facilitates differentiation of the C6 and C7 positions, resulting in a completely regioselective synthetic route. Biological testing of intermediates and some analogs provides some insights into the structure activity relationships and their effects on SHIP1 agonist activity."

Synthetic studies on K204, a potent new SHIP1 agonist (ACS-Sp 2019) - "...The increase in SHIP1 activity appears to be more significant than SHIP1 enzymatic activation by the known agonist AQX-1125. Initial synthetic studies on K204 has allowed for a preliminary evaluation of structure activity relationships. These studies are now moving towards the development of K204 analogs with increased potency and improved pharmacodynamic properties."