| Description | Seletalisib (UCB5857) (UCB5857) is a potent and specific PI3Kδ inhibitor (IC50: 12 nM). |
| In vitro | Seletalisib 能够在 B 细胞系中 BCR 激活后阻断 AKT 磷酸化。在用 Seletalisib 处理的 PBMCs 或其他细胞类型中没有观察到细胞性毒性迹象。Seletalisib 阻止活化 T 细胞产生多种细胞因子，并抑制 T 细胞向 Th1、Th2 和 Th17 亚型的分化。此外，Seletalisib 抑制 B 细胞的增殖和细胞因子释放。在人类全血测定中，Seletalisib 抑制 B 细胞激活时的 CD69 表达和抗 - IgE 介导的嗜碱细胞脱颗粒。 |
| In vivo | Seletalisib在大鼠中显著抑制TCR激活后的IL-2释放。在所有测试剂量中观察到抑制作用，剂量≥1 mg/kg时几乎完全抑制。Seletalisib具有强大的体内效果，估算的IC50值<10 nM。 |
| Cell experiments | 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. |
| Animal experiments | 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. |
| Target activity | PI3Kδ:12 nM |
| Synonyms | UCB5857 |
| molecular weight | 482.85 |
| Molecular formula | C23H14ClF3N6O |
| CAS | 1362850-20-1 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 80 mg/mL (165.69 mM) |
| References | 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. |