biostudies-literatureLemm EACancer Research UKWorldwide Cancer ResearchKay Kendall Leukaemia FundBlood Cancer UKSouthampton Experimental Cancer Medicine and Cancer Research Centres1700-1711https://www.ebi.ac.uk/biostudies/studies/S-EPMC7124891biostudies-literatureUnknown26(7)<h4>Purpose</h4>PI3K signaling is a common feature of B-cell neoplasms, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), and PI3K inhibitors have been introduced into the clinic. However, there remains a clear need to develop new strategies to target PI3K signaling. PI3K activity is countered by Src homology domain 2-containing inositol-5'-phosphatase 1 (SHIP1) and, here, we have characterized the activity of a novel SHIP1 activator, AQX-435, in preclinical models of B-cell malignancies.<h4>Experimental design</h4><i>In vitro</i> activity of AQX-435 was evaluated using primary CLL cells and DLBCL-derived cell lines. <i>In vivo</i> activity of AQX-435, alone or in combination with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, was assessed usiClinical cancer research : an official journal of the American Association for Cancer ResearchPreclinical Evaluation of a Novel SHIP1 Phosphatase Activator for Inhibition of PI3K Signaling in Malignant B Cells.PMC712489123669UNCE/MED/01616004140451600313-0267C24563/A15581GACR17-14007SA18087A23669C34999/A18087KKL01681800929370C2750/A23669A15581Stevenson FKKarolova JLemm EAGebreselassie YCarter MJHarwig CForconi FSteele AJKarydis LCragg MWilliamson CTValle-Argos BRichter JHelman KWeston-Bell NJCross JKlener PPettigrew JMackenzie LPackham GSmith LDSvaton MLenz GfalsePreclinical Evaluation of a Novel SHIP1 Phosphatase Activator for Inhibition of PI3K Signaling in Malignant B Cells.<h4>Purpose</h4>PI3K signaling is a common feature of B-cell neoplasms, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), and PI3K inhibitors have been introduced into the clinic. However, there remains a clear need to develop new strategies to target PI3K signaling. PI3K activity is countered by Src homology domain 2-containing inositol-5'-phosphatase 1 (SHIP1) and, here, we have characterized the activity of a novel SHIP1 activator, AQX-435, in preclinical models of B-cell malignancies.<h4>Experimental design</h4><i>In vitro</i> activity of AQX-435 was evaluated using primary CLL cells and DLBCL-derived cell lines. <i>In vivo</i> activity of AQX-435, alone or in combination with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, was assessed usi2020-01-01T00:00:00Z2020 Apr2025-04-05T13:25:38.121Z2020-10-08T07:16:09ZS-EPMC71248913183156210.1158/1078-0432.CCR-19-220210.1158/1078-0432.ccr-19-2202