AQX-435

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

AQX-435 reduces CLL cell viability in a dose-dependent manner^[1].
AQX-435-induced (5-30 µM; 24 hours) apoptosis is 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].

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].

References:
[1]. Lyoyd F. MACKENZIE, et al. Ship1 modulators and methods related thereto.WO2014110036A1.
[2]. Lemm EA, et al. Preclinical Evaluation of a Novel SHIP1 Phosphatase Activator for Inhibition of PI3K Signaling in Malignant B Cells. Clin Cancer Res. 2020;26(7):1700-1711.