IRAK4-IN-28 (compound 42), an orally-active IRAK4 inhibitor (IC50=8.9 nM), exhibits strong binding affinity with a Kd of 0.58 nM for the target enzyme. It is utilized for research purposes in the study of inflammation and autoimmune diseases [1].

IRAK4-IN-28 does not inhibit cytochrome P450 enzymes CYP1A2, CYP2D6, CYP3A4, and hERG, indicating favorable safety and 'drug-like' properties [1]. However, it inhibits CYP2C9 and CYP2C19 with IC50 values of 12 μM and 2.7 μM, respectively [1]. It also exhibits high plasma protein binding in humans and rats (99.8% and 97.2%, respectively) [1]. Furthermore, IRAK4-IN-28 (1 h) dose-dependently suppresses LPS-induced TNF-α and IL-6 expression at mRNA and protein levels [1].

IRAK4-IN-28 (compound 42) exhibits favorable pharmacokinetic data in a rat model, with an oral bioavailability utilization rate of 68% [1]. A single oral dose of IRAK4-IN-28 at 50 or 100 mg/ml significantly reduces LPS-induced TNF-α and IL-6 cytokine release in a mouse model [1].