Seletalisib (UCB5857) is potent and selective PI3Kδ inhibitor with an IC50 of 12 nM.
Seletalisib is a potent, ATP-competitive and highly selective PI3Kδ inhibitor able to block AKT phosphorylation following activation of the BCR in a B-cell line. Seletalisib inhibits N-formyl peptides (fMLP)-stimulated but not phorbol myristate acetate (PMA)-stimulated superoxide release from human neutrophils consistent with a PI3Kδ-specific activity. No indications of cytotoxicity are observed in PBMCs or other cell types treated with seletalisib. seletalisib blocks human T-cell production of several cytokines from activated T-cells. Seletalisib inhibits T-cell differentiation to Th1, Th2, and Th17 subtypes. Additionally, seletalisib inhibits B-cell proliferation and cytokine release. In human whole blood assays, seletalisib inhibits CD69 expression upon B-cell activation and anti-IgE-mediated basophil degranulation[1].
Seletalisib significantly inhibits IL-2 release following TCR stimulation in the rat. The inhibition is observed at all tested doses of seletalisib with almost complete inhibition reached at dose levels ≥1 mg/kg. Seletalisib has potent in vivo effects with an estimated IC50 value of <10 nM[1].
[1]. Allen RA, et al. Seletalisib: Characterization of a Novel, Potent, and Selective Inhibitor of PI3Kδ. J Pharmacol Exp Ther. 2017 Apr 25. pii: jpet.116.237347.