Acetylcysteinamide

Acetylcysteinamide
Identifiers
	IUPAC name (2R)-2-Acetamido-3-sulfanylpropanamide;
CAS Number	38520-57-9 ; 15394-73-7 (racemic);
PubChem CID	9942232;
DrugBank	DB14480;
ChemSpider	74304;
UNII	4N69717RKW;
CompTox Dashboard (EPA)	DTXSID30436398 ;
ECHA InfoCard	100.211.696
Chemical and physical data
Formula	C5H10N2O2S
Molar mass	162.21 g·mol−1
3D model (JSmol)	Interactive image;
Density	1.227 g/cm3
Boiling point	308 °C (586 °F)
Solubility in water	22 mg/mL (20 °C)
	SMILES SC[C@H](C(=O)N)NC(=O)C;
	InChI InChI=1S/C5H10N2O2S/c1-3(8)7-4(2-10)5(6)9/h4,10H,2H2,1H3,(H2,6,9)(H,7,8)/t4-/m1/s1; Key:UJCHIZDEQZMODR-SCSAIBSYSA-N;

N-Acetylcysteine amide (abbrev. NACA, AD4 and also known as acetylcysteinamide) is an amide derivative of N-acetylcysteine (NAC) that appears to have better blood–brain barrier permeability and bioavailability possessing potential antioxidant and anti-inflammatory activity^[1]^[2]

When administered, NACA increases glutathione levels. Glutathione neutralizes reactive oxygen species, reduces oxidative stress, and prevents induced cell damage and apoptosis. NACA has increased lipophilicity and membrane permeability compared to NAC.^[2]

Chemical designation

This compound belongs to a class of experimental compounds known as N-acyl-alpha-amino acids and their derivatives. These are compounds containing an alpha-amino acid (or its derivative) with an acyl group on the terminal nitrogen atom.^[3]

Pharmacokinetics and pharmacodynamics

The pharmacokinetics of NACA remain unclear or unstudied. It is an amide derivative of NAC that is rapidly converted to NAC after systemic administration.

The bioavailability of NACA is significantly higher than NAC (67% and 15%,).^[4]

Its mechanism of action involves replenishment of glutathione (GSH), a major antioxidant, and direct neutralization of reactive oxygen species.^[4]

References

^ Sunitha K, Hemshekhar M, Thushara RM, Santhosh MS, Yariswamy M, Kemparaju K, et al. (May 2013). "N-Acetylcysteine amide: a derivative to fulfill the promises of N-Acetylcysteine". Free Radical Research. 47 (5): 357–367. doi:10.3109/10715762.2013.781595. PMID 23472882. S2CID 207517783.
^ ^a ^b "N-Acetylcysteine amide". PubChem. U.S. National Library of Medicine. Retrieved 2025-09-13.
^ "Acetylcysteine amide". go.drugbank.com. Retrieved 2025-09-09.
^ ^a ^b He R, Zheng W, Ginman T, Ottosson H, Norgren S, Zhao Y, et al. (February 2020). "Pharmacokinetic profile of N-acetylcysteine amide and its main metabolite in mice using new analytical method". European Journal of Pharmaceutical Sciences. 143 105158. doi:10.1016/j.ejps.2019.105158. PMID 31740394.

[1] Sunitha K, Hemshekhar M, Thushara RM, Santhosh MS, Yariswamy M, Kemparaju K, et al. (May 2013). "N-Acetylcysteine amide: a derivative to fulfill the promises of N-Acetylcysteine". Free Radical Research. 47 (5): 357–367. doi:10.3109/10715762.2013.781595. PMID 23472882. S2CID 207517783.

[PubChem-2] "N-Acetylcysteine amide". PubChem. U.S. National Library of Medicine. Retrieved 2025-09-13.

[3] "Acetylcysteine amide". go.drugbank.com. Retrieved 2025-09-09.

[He-4] He R, Zheng W, Ginman T, Ottosson H, Norgren S, Zhao Y, et al. (February 2020). "Pharmacokinetic profile of N-acetylcysteine amide and its main metabolite in mice using new analytical method". European Journal of Pharmaceutical Sciences. 143 105158. doi:10.1016/j.ejps.2019.105158. PMID 31740394.

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