NACET

NACET (N-acetyl-L-cysteine ethyl ester; CAS 59587-09-6; molecular formula C7H13NO3S; molecular weight 191.25) is the ethyl ester prodrug of N-acetylcysteine (NAC), developed at the University of Southern California and at Italian academic groups during the 2000s as a lipophilic alternative to NAC with markedly improved cellular and central nervous system bioavailability. The parent NAC is a polar carboxylic acid with low oral bioavailability (approximately 6 to 10 percent), poor blood-brain barrier penetration, and limited intracellular accumulation; NACET is a neutral ester at physiological pH, crosses cell membranes by passive diffusion, and is hydrolyzed intracellularly by ubiquitous esterases to release NAC inside the cell. Published in vitro studies report cellular glutathione (GSH) elevation 30 to 50 percent above baseline after NACET exposure compared to less than 10 percent for equimolar NAC, owing to the difference in cellular delivery. Published rodent in vivo work reports brain GSH elevation after oral NACET that is not detectable after equimolar oral NAC, consistent with the BBB-penetration argument. The pharmacological consequence is that NACET delivers the antioxidant and glutathione-precursor activity of NAC at lower oral doses with central nervous system exposure. Reported applications in research include neuroprotection, oxidative stress modulation, and as a research tool for cysteine delivery in cell culture. Human pharmacokinetic data are limited and no large clinical trials have been published. The compound is not approved by FDA or EMA for any indication. NAC itself is approved as an antidote for acetaminophen overdose and as a mucolytic; the ester form is sold only as a research-grade compound or supplement. Stability is moderate at room temperature; refrigerated storage is preferred for solid material.