Nemiralisib

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

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1mg

￥762.00

610.00

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5mg

￥1212.00

970.00

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10mg

￥2062.00

1650.00

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25mg

￥4200.00

3360.00

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50mg

￥7662.00

6130.00

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100mg

￥12825.00

10260.00

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200mg

￥0.00

0.00

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500mg

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Background

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

GSK-2269557 has low oral bioavailability (F=2%) and in vivo clearance of 28 mL/min/kg but has a high volume of distribution of 6.3 L/kg. GSK-2269557 induces concentration-dependent increases in QT interval and Tp-e at 0.3 and 1 μM (1 and 0.5 Hz) and an increase in QRS at 1 μM (2 Hz), however, no treatment-related torsades de pointes (TdP) arrhythmias are observed. In a disease relevant brown Norway rat acute OVA model of Th2 driven lung inflammation, GSK-2269557 is shown to protect against eosinophil recruitment with an ED50 of 67 μg/kg and dose-dependently reduces recruitment of all leukocyte subpopulations and IL-13 in the lungs[1].

[1] Down K, et al. J Med Chem. 2015, 58(18):7381-99.

Protocol

Animal experiment:

Rats[1]In vivo pharmacokinetics is tested in Sprague Dawley male rats. Compounds (e.g., Nemiralisib) are administered discretely by the oral or intravenous routes, at a dose level of 3 and 1 mg/kg respectively (n=2 rats/route). Compounds (e.g., Nemiralisib) are formulated as a solution in DMSO:PEG200:water (5:45:50 v/v/v) at a dose volume of 6 (oral) and 2 (intravenous) mL/kg. All animals are serially bled from the tail vein and blood samples collected over a time-course of 0-7 h are submitted to LC-MS/MS analysis for the quantification of the parent compound. The main pharmacokinetic parameters are estimated by non-compartmental analysis.

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.