AQX-435

AQX-435 is a potent SHIP1 activator. AQX-435 reduces PI3K activation downstream of the B-cell receptor (BCR) and induces apoptosis of malignant B cells, and reduces lymphoma growth[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphatase

Research Areas >> Inflammation/Immunology

AQX-435 reduces CLL cell viability in a dose-dependent manner[1]. AQX-435 (5-30 µM; 24 hours)-induced apoptosis was mediated via caspases since AQX435 induced PARP cleavage[1]. AQX-435 effectively inhibits PI(3,4,5)P3-mediated signaling downstream of the BCR in CLL and DLBCL cells[1]. AQX-435 and ibrutinib combine effectively to enhanced inhibition of BCR signaling. AQX-435 induced TMD8 cell apoptosis in vitro with an IC50 of ~2 µM. AQX-435 reduces anti-IgM-induced AKT phosphorylation and induces apoptosis in DLBCL cells[1]. Cell Viability Assay[1] Cell Line: Chronic lymphocytic leukemia (CLL) cells Concentration: 5-30 µM Incubation Time: 24 hours Result: Reduced CLL cell viability in a dose-dependent manner.

AQX-435 (10 mg/kg; i.p.; 5 days) significantly reduced the volume of TMD8 tumors[1]. AQX-435 (50 mg/kg; ip) inhibits DLBCL PDX tumors growth[1]. AQX-435 reduced AKT phosphorylation and growth of DLBCL in vivo and cooperated with ibrutinib for tumor growth inhibition[1]. Animal Model: NOD.Cg-Prkdc scidIl2rgtm1Wjl/SzJ mice (NSG mice) (TMD8 tumors)[1] Dosage: 10 mg/kg Administration: I.p.; in 7-day cycles each comprising 5 days of AQX-435 followed by 2 days with no drug Result: Reduced the volume of TMD8 tumors.

[1]. Lyoyd F. MACKENZIE, et al. Ship1 modulators and methods related thereto.WO2014110036A1.