Seletalisib 是一种有效的、选择性的PI3Kδ抑制剂，其 IC50=12 nM。

Seletalisib (UCB5857) is a potent and specific PI3Kδ inhibitor (IC50: 12 nM).

Seletalisib is able to block AKT phosphorylation following activation of the BCR in a B-cell line. 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.

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.

Seletalisib is dissolved 1 mM solution in DMSO, and tested in a concentration-response, to explore the effects of PI3Kδ-specific inhibition compared with complete inhibition of class I PI3K signaling. In addition, seletalisib is tested in the BioMap BT cell system at concentrations of 1000, 100, 10, and 1 nM. An activity profile is generated based on the effect of the compounds on the levels of cellular readouts, including cytokines, growth factors, adhesion molecules, and proliferation endpoints.

Rats are dosed with Seletalisib (0.1-10 mg/kg in 500 μL volume) or vehicle via oral gavage 30 min prior to i.v. administration of anti- CD3 antibody administered in a 200 μL dose volume. The vehicle is methylcellulose or saline for oral and i.v. administration, respectively. Seletalisib levels and IL-2 levels are measured.

1362850-20-1

C23H14ClF3N6O

482.85

UCB5857

DMSO:80 mg/mL (165.69 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years