(Rac)-PF-184

(Rac)-PF-184 is a potent inhibitory factor-κB kinase 2 (IKK-2) inhibitor with an IC₅₀ of 37 nM. (Rac)-PF-184 has anti-inflammatory effects^[1]. IC50 & Target: IC₅₀: 37 nM (IKK-2)^[1] In Vitro: (Rac)-PF-184 has slow dissociation kinetics with a T_1/2 of 6.7 h from rhIKK-2, very low oral bioavailability (5%), high intravenous clearance (59 ml/min/kg), and high P450 metabolism in human liver microsomes^[1].
(Rac)-PF-184 binds tightly to endogenous IKK-2 and shows extended inhibition of kinase activity and cytokine production^[1].
(Rac)-PF-184 shows a concentration-dependent inhibition on LPS- and IL-1β-induced production of inflammatory mediators in a variety of human disease-relevant cells^[1].
(Rac)-PF-184 (0.001-10 µM, 1 h) inhibits IL-1β-induced TNF-α in a concentration-dependent manner with maximal efficacies of 94% and relative potencies of 163 nM^[1].
(Rac)-PF-184 inhibits LPS-induced cytokine production from rat alveolar macrophages and blocked p65 nuclear translocation^[1]. In Vivo: (Rac)-PF-184 (0.3-2.5 mg; i.t.; once) blocks neutrophil infiltration and BAL cell cytokine production^[1].