AQX-435

• CAT Number: I022364
• CAS Number: 1619983-52-6
• Molecular Formula: C27H34N2O4
• Molecular Weight: 450.57
• Purity: ≥95%
• Synonyms: N-[(2R,3S,4S,4aS,8aS)-4-(3,5-dihydroxybenzoyl)-3,4a,8,8-tetramethyl-1,2,3,4,5,6,7,8a-octahydronaphthalen-2-yl]pyridine-3-carboxamide
• InChI: InChI=1S/C27H34N2O4/c1-16-21(29-25(33)17-7-5-10-28-15-17)14-22-26(2,3)8-6-9-27(22,4)23(16)24(32)18-11-19(30)13-20(31)12-18/h5,7,10-13,15-16,21-23,30-31H,6,8-9,14H2,1-4H3,(H,29,33)/t16-,21-,22+,23-,27+/m1/s1
• InChIKey: JBBCDNNDYGLMOE-LZITZJIASA-N
• SMILES: CC1C(CC2C(CCCC2(C1C(=O)C3=CC(=CC(=C3)O)O)C)(C)C)NC(=O)C4=CN=CC=C4

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[1][2].
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].

Reference

[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.
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