N-acetylcysteine Pharmacology and Applications in Rare Diseases—Repurposing an Old Antioxidant

Siddhee A. Sahasrabudhe, Marcia R. Terluk, Reena V. Kartha

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


N-acetylcysteine (NAC), a precursor of cysteine and, thereby, glutathione (GSH), acts as an antioxidant through a variety of mechanisms, including oxidant scavenging, GSH replenishment, antioxidant signaling, etc. Owing to the variety of proposed targets, NAC has a long history of use as a prescription product and in wide-ranging applications that are off-label as an over-the-counter (OTC) product. Despite its discovery in the early 1960s and its development for various indications, systematic clinical pharmacology explorations of NAC pharmacokinetics (PK), pharmacodynamic targets, drug interactions, and dose-ranging are sorely limited. Although there are anecdotal instances of NAC benefits in a variety of diseases, a comprehensive review of the use of NAC in rare diseases does not exist. In this review, we attempt to summarize the existing literature focused on NAC explorations in rare diseases targeting mitochondrial dysfunction along with the history of NAC usage, approved indications, mechanisms of action, safety, and PK characterization. Further, we introduce the research currently underway on other structural derivatives of NAC and acknowledge the continuum of efforts through pre-clinical and clinical research to facilitate further therapeutic development of NAC or its derivatives for rare diseases.

Original languageEnglish (US)
Article number1316
Issue number7
StatePublished - Jul 2023

Bibliographical note

Funding Information:
S.A.S. and M.R.T. report no financial disclosure and conflict of interest in reference to this work. R.V.K. has received investigator-initiated funds from Pfizer Inc., Sanofi, and the NIH.

Publisher Copyright:
© 2023 by the authors.


  • antioxidant
  • mechanism of action
  • pharmacology
  • rare diseases
  • repurposing

PubMed: MeSH publication types

  • Journal Article
  • Review


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