PAPA NONOate

PAPA NONOate is a diazeniumdiolate small molecule NO donor with a reported NO release half-life of 77 min (22-25°C). NO release from PAPA NONOate has demonstrated regulation of caspase-3 activity and suppression of the caspase apoptotic cascade via inhibition of S-nitrosylation of the Cys-163 residue on caspase-3. In NO-vacant NT2N cells, NO release from PAPA NONOate produced cell death through apoptotic signaling, as contrasted with the necrotic injury produced by peroxynitrite exposure. NO release from PAPA NONOate is shown to increase cGMP in a model of ischemic lung injury, suggesting that the protective effects of NO against ischemic injury are cGMP-mediated. PAPA NONOate also demonstrated inhibition of protein synthesis in A375 melanoma cells through release of NO, inhibiting thymidine incorporation by 50% (44 μM) and producing a cytostatic effect.