Animal experiment:

Rats[1] In the TLR driven in vivo model, female Lewis rats are dosed with either vehicle or IRAK4-IN-1 (Compound 23; 3, 10, 30, and 100 mg/kg; p.o.) dosed at 1 h prior to stimulation with Resiquimod, R848 (5 mg/kg, IP). At 1.5 h post R848 stimulation, blood samples are obtained from the animals and cytokine levels are measured.

IRAK4-IN-1 is an interleukin-1 receptor associated kinase 4 (IRAK4) inhibitor with an IC50 of 7 nM.

The in vitro metabolic stability profiles of IRAK4-IN-1 (Compound 23) is measured, with EC50 of 2300 nM for the rat whole blood (RWB) [1].

Oral pharmacokinetic studies of IRAK4-IN-1 (Compound 23) show it to have high bioavailability of 73% and low plasma clearance(Clp=22 mL/min/kg) leading to a reasonable half-life of 1.3 h[1].

[1]. Smith GF, et al. Identification of quinazoline based inhibitors of IRAK4 for the treatment of inflammation. Bioorg Med Chem Lett. 2017 Jun 15;27(12):2721-2726.