6-(1H-indol-4-yl)-4-(5-((4-isopropylpiperazin-1-yl)methyl)oxazol-2-yl)-1H-indazole

Nemiralisib (GSK2269557 free base) is a potent and highly selective PI3Kδ inhibitor with a pKi of 9.9.

Nemiralisib, also known as GSK-2269557, is a potent and selective PI3Kδ inhibitor (pKi=9.9).

Nemiralisib has relatively low oral bioavailability (F=2%), in vivo clearance is 28 mL/min/kg, but high volume distribution, 6.3 L/kg. 0.3-1 μMGSK-2269557 induction concentration Dependent QT interval and T_pe prolongation, 1 μM GSK-2269557 resulted in prolongation of the ORS wave, during which no torsades de pointes arrhythmia was observed.

PI3Kδ: 9.9 (pKi); PI3Kγ: 5.2 (pIC₅₀); PI3Kα: 5.3 (pIC₅₀); PI3Kβ: 5.8 (pIC₅₀)

[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. DOI:10.1021/acs.jmedchem.5b00767