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Phosphoinositide 3-kinases (PI3K) are key signaling enzymes regulating cellular survival, development, and function. Expression of the PI3K δ isoform is largely restricted to leukocytes and it plays a key role in immune cell development and function. Seletalisib is a novel small-molecule inhibitor of PI3K δ that was evaluated in biochemical assays, cellular assays of adaptive and innate immunity, and an in vivo rat model of inflammation. Our findings show that seletalisib is a potent, ATP-competitive, and selective PI3K δ inhibitor able to block protein kinase B (AKT) phosphorylation following activation of the B-cell receptor in a B-cell line. Moreover, seletalisib inhibited N -formyl peptide–stimulated but not phorbol myristate acetate–stimulated superoxide release from human neutrophils, consistent with a PI3K δ -specific activity. No indications of cytotoxicity were observed in peripheral blood mononuclear cells (PBMCs) or other cell types treated with seletalisib. Findings from cellular assays of adaptive immunity demonstrated that seletalisib blocks human T-cell production of several cytokines from activated T-cells. Additionally, seletalisib inhibited B-cell proliferation and cytokine release. In human whole blood assays, seletalisib inhibited CD69 expression upon B-cell activation and anti-IgE-mediated basophil degranulation. Seletalisib showed dose-dependent inhibition in an in vivo rat model of anti-CD3-antibody-induced interleukin 2 release. Collectively, these data characterize seletalisib as a selective PI3K δ inhibitor and potential therapeutic candidate for the treatment of B-cell malignancies and autoimmune diseases driven by dysregulated proinflammatory cytokine secretion.

Activation of the tyrosine kinase ZAP 70 has been shown to be crucial to the transduction of the T-cell receptor signalling pathway, which leads ultimately to proliferation, cytokine gene expression and T-cell effector functions. A series of 2-phenylaminopyrimidines have been identified as potent and selective inhibitors of ZAP 70.

The cuticular proteins of second-stage juveniles and adult females of the plant parasitic nematode Meloidogyne incognita have been investigated by surface radio-iodination and detergent solubilization techniques. This approach revealed a restricted number of surface proteins which were stage-specific after extraction with either sodium deoxycholate or sodium dodecyl sulphate (SDS)/β-mercaptoethanol. SDS-polyacrylamide gel electrophoresis of radiolabelled proteins detected some proteins from both stages that were superficially located on the nematode cuticle. These molecules may offer targets for immunological detection of this pest and may also play a role in the host-parasite relationship.