PF 184 is a potent and selective IKK-2 inhibitor (IC50 = 37 nM). Displays selectivity over 85 other kinases. Inhibits IL-1β-induced TNF-α in a steroid-insensitive in vitro model of oxidative stress.
in vivo
(Rac)-PF-184 (0.3-2.5 mg; i.t.; once) blocks neutrophil infiltration and BAL cell cytokine production[1].
Animal Model:
Fasted male Sprague-Dawley rats (350 g) placed into a chamber connected to a large volume nebulizer filled with 20 ml of 1 mg/mL solution of LPS[1]
Dosage:
0.3-2.5 mg
Administration:
Nano suspension and administered intratracheally in a volume of 100 μL, 60 min before aerosolized LPS
Result:
Resulted in a comparable attenuation of total cell and PMN cell infiltration 4 h after LPS exposure. Dose-dependently inhibited cell infiltration with EC50 values of 1 mg. Dose-dependently suppressed BAL fluid TNF- and PGE2 levels comparable with cell infiltration. Inhibited p65 translocation. Showed long-lasting activity.
