PNRI-299

PNRI-299 is a selective AP-1 transcription inhibitor with an IC₅₀ of 20 uM. PNRI-299 is a selective APE/Ref-1 inhibitor. PNRI-299 has no effect on NF-κB transcription or thioredoxin (up to 200 uM). PNRI-299 significantly reduces airway eosinophil infiltration, mucus hypersecretion, edema, and IL-4 levels in a mouse asthma model^[1][2][3]. In Vitro: PNRI-299 specifically reacts with Ref-1, inhibits AP-1 transcription, and overexpression of the molecular target. Ref-1 attenuates PNRI-299 inhibition of AP-1 transcription. PNRI-299 interacts with the redox nucleophile Cys-65, to aid in the interpretation of structure activity relationships (SARs)^[1].
In Vivo: PNRI-299 (intranasal; 0.75 or 2.0 mg/kg; 30 min before OVA on days 25-27) reduces the airway inflammatory cell infiltration (arrows) and mucus release in ovalbumin (OVA)-treated (i.p.; 100 μg) female BALB/c mice aged 6-8 wk)^[1].
PNRI-299 (3, 10?mg/kg; iv; 5?min before reperfusion) has no significant effect on the translocation of NF-κB in male C57/BL6 mice (8-10 weeks). PNRI-299 has little effect on the inflammatory response that follows intestinal I/R injury^[2].