p110δ 选择性抑制剂;p110δ Selective Inhibitors;;InformationGSK2292767 is a potent and selectivePI3Kδinhibitor.TargetsPI3KδIn vivoGSK2292767 is highly selective for PI3Kδ over the closely related isoforms and is active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.
体内研究:
GSK2292767 exhibits high clearance (50 mL/min/kg) in vivo and low oral bioavailability (F < 2%) in a rat PK study. GSK2292767 (0.01-1 μM) has no e ect on QT interval, Tp e, or QRS and no signi cant risk of TdP arrhythmias in a rabbit cardiac ventricular wedge assay. GSK2292767 protects against eosinophil recruitment with an ED50 of 35 μg/kg in the brown Norway rat acute OVA model of Th2 driven in ammation in the lungs of rats.
参考文献:
1. Down K, et, al. Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease. J Med Chem. 2015 Sep 24; 58(18): 7381-99.