PNRI-299 is a selective AP-1 transcription inhibitor with IC50 of 20 uM without affecting NF-kappaB transcription (up to 200 uM) or thioredoxin (up to 200 uM).IC50 value: 20 uM [1]Target: AP-1 inhibitorin 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).in vivo: Treatment with PNRI-299 significantly decreased the influx of eosinophils, monocytes, and macrophages (no significant reduction of lymphocytes was observed) into the lung interstitium and bronchoalveolar lavage fluid, and airway mucus and edema observed in OVA-treated mice.PNRI-299 reduces the pathophysiological responses seen in this murine model of allergic asthma [1]. PNRI-299 had no effects on the inflammatory changes or lethality induced by I/R injury [2].
[1]. Nguyen C, et al. Chemogenomic identification of Ref-1/AP-1 as a therapeutic target for asthma. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1169-73. [2]. Souza DG, et al. NF-kappaB plays a major role during the systemic and local acute inflammatory response following intestinal reperfusion injury. Br J Pharmacol. 2005 May;145(2):246-54.