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Chemical Structure| 616-91-1 Chemical Structure| 616-91-1

Structure of Acetylcysteine
CAS No.: 616-91-1

Chemical Structure| 616-91-1

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Acetylcysteine is an inhibitor of ROS and the production of TNF. It is a pharmaceutical drug and nutritional supplement used as mucolytic agent.

Synonyms: NAC; N-Acetylcysteine; N-Acetyl-L-cysteine

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Wang, Shengmei ; Ma, Ding ; Yang, Minghua ; Zhang, Ye ; Wang, Shengfeng ; Zhou, Wenhu

Abstract: Chemotherapy remains a primary treatment option for hepatocellular carcinoma (HCC), yet its clinical benefits are often unsatisfactory. Utilizing arsenic trioxide (ATO) as a model, this study elucidates the role of autophagy inhibition in modulating the cellular response to chemotherapy, shifting cell death from apoptosis to pyroptosis via the caspase-3–GSDME pathway, thereby augmenting the anti-tumor efficacy. Building upon these findings, an ATO nanomedicine delivery system capable of autophagy inhibition to promote pyroptosis for enhanced tumor treatment was developed. Folic acid-modified albumin served as the stabilizer for nano selfassemblies formed through ion pairing between Mn2+ and ATO, encapsulating DNAzyme (Dz) targeting Beclin 1, a key autophagy regulator. Characterization studies confirmed efficient encapsulation of ATO and Dz within nanoparticles, designed to disintegrate in the intracellular microenvironment, releasing the all-active components, i.e., ATO, Mn2+, and Dz. Mn2+ acted as a metal cofactor to activate Dz for Beclin 1 mRNA cleavage, inhibiting autophagy and augmenting ATO-induced cell pyroptosis. Elevated cell pyroptosis levels not only enhance ATO’s direct tumor cell killing capacity but also trigger anti-tumor immune responses, synergistically enhancing efficacy. Upon intravenous injection, the nanomedicine accumulated in tumor tissue and targeted liver cancer cells. Compared to free ATO, the nanomedicine exhibited significantly improved in vivo anti-tumor effects, achieving a 100% 45-day survival rate in mice with favorable biosafety profiles. This study offers novel insights into tumor chemotherapy sensitization and presents a promising strategy for ATO nanoformulation development.

Keywords: Nanoparticles ; Cell death ; Chemotherapy ; Targeting ; Tumor immunity ; Drug delivery ; Arsenic trioxide ; Hepatocellular carcinoma

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Li, Chengyu ; Liu, Zhaojun ; Zhu, Linjie ; Wu, Gang ; Fu, Chen ; Li, Hongmin , et al.

Abstract: HMGB1, one of the most abundant nuclear non-histone proteins, also performs extracellular functions, and its nuclear export mechanisms have been extensively studied. Here, a novel mechanism of nuclear export for HMGB1 driven by lactylation is proposed. In addition, it is revealed that hypoxia-induced lactylation of HMGB1 facilitates its nuclear export in a complex with TIAR, promoting stress granule (SG) formation in the cytosol. Mass spectrometry revealed 12 lysine residues in HMGB1 undergoing lactylation, with K172 and K177 being the most susceptible. Functional studies using lysine-to-arginine mutants (K→R) demonstrated that lactylation at K177 is crucial for HMGB1-TIAR complex export, as K177R mutation completely blocked this export and subsequent SG formation. Notably, this lactylation-mediated mechanism is specific to hypoxic stress, while other stressors, such as sodium arsenite exposure and heat shock, triggered TIAR nuclear export and SG assembly independently of HMGB1. These findings reveal a previously unrecognized role of HMGB1 lactylation in mediating nuclear export and SG formation under hypoxia.

Keywords: HMGB1 ; hypoxic stress granules ; lactylation ; nuclear export ; TIAR

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Ievtukhov, Vladyslav ; Zadykowicz, Beata ; Blazheyevskiy, Mykola Ye. ; Krzyminski, Karol ;

Abstract: Biologically active compounds containing sulfhydryl groups (RSHs: N-acetyl-L-cysteine, D-penicillamine, glutathione and acetylthiocholine chloride) were used to develop a luminometric method for their quantification. The title substrate capable of chemiluminescence (CL) was isolated in a highly pure state as a chloride salt (99.9% using RP-HPLC) and identified using mass spectrometry (ESI Q-TOF) and 1H NMR spectroscopy. The cation included in the salt, 9-CMA+, underwent oxidation in an alk. environment containing RSHs by mol. oxygen, generating CL of various intensities, with no need for the use of hydrogen peroxide. The amount of produced light was linearly proportional to the content of investigated analytes in the system over the concentration range ∼0.2-2μM, with the detection limits in the range 0.19-1.73μM. The mechanism of chemiluminogenic oxidation of 9-CMA+ in the presence of RSHs and mol. oxygen is proposed, using computational methods at the d.-functional theory level. The presence of RSHs in an alk. medium seems to be crucial to produce hydroperoxide anions (-OOH), which initiate the 'light path' of 9-CMA+ transformations, ending with the excretion of electronically excited mols. of 10 methyl-acridan-9-one.

Keywords: 9-cyano-10-methylacridinium cation ; chemiluminescence analysis ; DFT methods ; MS and NMR spectroscopy ; thiol nucleophiles

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Alternative Products

Product Details of Acetylcysteine

CAS No. :616-91-1
Formula : C5H9NO3S
M.W : 163.19
SMILES Code : SC[C@@H](C(O)=O)NC(C)=O
Synonyms :
NAC; N-Acetylcysteine; N-Acetyl-L-cysteine
MDL No. :MFCD00004880
InChI Key :PWKSKIMOESPYIA-BYPYZUCNSA-N
Pubchem ID :12035

Safety of Acetylcysteine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • TNF-α

In Vitro:

Cell Line
Concentration Treated Time Description References
Neutrophils 1 mM 30 min To assess the effect of NAC on NET formation, results showed that NAC reduced PMA-induced NET formation. Blood Adv. 2020 Jan 28;4(2):312-321.
LS174T 2.5-40 mM 72 h Acetylcysteine significantly inhibited the proliferation of LS174T cells, particularly at higher concentrations. J Exp Clin Cancer Res. 2014 Nov 12;33(1):92.
HT29-5M21 1-75 mM 72 h Acetylcysteine significantly inhibited the proliferation of HT29-5M21 cells, particularly at higher concentrations. J Exp Clin Cancer Res. 2014 Nov 12;33(1):92.
HT29-5F12 1-75 mM 72 h Acetylcysteine significantly inhibited the proliferation of HT29-5F12 cells, particularly at higher concentrations. J Exp Clin Cancer Res. 2014 Nov 12;33(1):92.
KATO-III 1-100 mM 72 h Acetylcysteine significantly inhibited the proliferation of KATO-III cells, particularly at higher concentrations. J Exp Clin Cancer Res. 2014 Nov 12;33(1):92.
MKN45 1-100 mM 72 h Acetylcysteine significantly inhibited the proliferation of MKN45 cells, particularly at higher concentrations. J Exp Clin Cancer Res. 2014 Nov 12;33(1):92.
Panc-1 cells 1 mM 72 h To evaluate the effect of NAC/Cu(II) on Panc-1 cells, it was found that NAC/Cu(II) significantly reduced cell viability. Cancer Lett. 2010 Dec 8;298(2):186-94.
T47D cells 1 mM 72 h To evaluate the effect of NAC/Cu(II) on T47D cells, it was found that NAC/Cu(II) significantly reduced cell viability. Cancer Lett. 2010 Dec 8;298(2):186-94.
MDA-MB-231 cells 1 mM 72 h To evaluate the effect of NAC/Cu(II) on MDA-MB-231 cells, it was found that NAC/Cu(II) significantly reduced cell viability. Cancer Lett. 2010 Dec 8;298(2):186-94.
A2780 cells 1 mM 72 h To evaluate NAC as a potential metal ionophore/shuttle, it was found that NAC is cytotoxic only in the presence of copper and inhibits cell growth by inducing apoptosis. Cancer Lett. 2010 Dec 8;298(2):186-94.
CF sputum 2.5 mM 30 min To compare the mucolytic effects of MUC-031 and NAC, MUC-031 was more effective in reducing the elastic modulus (G′) of sputum and acted faster. MUC-031 induced mucolysis in 69% of sputum samples within 15 min, compared to 25% for NAC. Eur Respir J. 2023 May 25;61(5):2202022.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice JAK2V617F knockin mouse model Oral 2 g/L Starting from 4 to 6 weeks of age, replenished weekly, continuous administration. To investigate the effect of NAC on thrombosis in MPN mice, results showed that NAC extended the lifespan of JAK2V617F mice and reduced thrombus formation. Blood Adv. 2020 Jan 28;4(2):312-321.
Mice ΒENaC-Tg mice Intratracheal instillation (adult mice) or intranasal instillation (neonatal mice) 131 mg/mL Three times in one day (acute experiment) or twice daily for two weeks (chronic experiment) To evaluate the mucolytic efficacy of MUC-031 in βENaC-Tg mice. Acute treatment significantly reduced airway mucus plugging and inflammation; chronic treatment sustained these reductions and improved survival. Eur Respir J. 2023 May 25;61(5):2202022.
BALB/c mice Hind leg muscle model Diet 5% Daily for 14 days To investigate the effect of dietary NAC on radical-induced structural changes in DNA, results showed that NAC significantly reduced the concentration of 8-OH-Gua and decreased the variance in the oxidative status of DNA. Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5937-41
Rats and mice Early-life stress (ELS) model and EAAC1 knockout mice Intraperitoneal injection 50 mg/kg and 150 mg/kg Once daily for 2 days NAC injection alleviated depressive-like behaviors in NMS model rats and reduced oxidative stress and neuroinflammation. In EAAC1-/- mice, NAC improved depressive-like behaviors but not impulsive behaviors. Int J Biol Sci. 2024 Oct 7;20(14):5450-5473

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT04278898 Autism Spectrum Disorder PHASE2 RECRUITING 2025-01-27 Stanford University School of ... More >>Medicine, Stanford, California, 94305, United States Less <<
NCT06546475 Psychosis PHASE4 NOT_YET_RECRUITING 2027-07-31 -
NCT01808521 Purpura, Thrombotic Thrombocyt... More >>openic|TTP Less << EARLY_PHASE1 COMPLETED 2025-07-17 Puget Sound Blood Center, Seat... More >>tle, Washington, 98104, United States Less <<
NCT06260566 Biliary Atresia PHASE1 NOT_YET_RECRUITING 2025-02-27 -
NCT02094625 Neuroectodermal Tumors, Primit... More >>ive|Liver Neoplasms|Osteosarcoma|Other Childhood Cancers Using Cisplatin-based Regimens Less << PHASE1 COMPLETED 2025-08-21 Childrens Hospital Los Angeles... More >>, Los Angeles, California, 90027, United States Less <<
NCT00211653 Kidney Failure PHASE1|PHASE2 COMPLETED 2025-11-06 Veterans Affairs Medical Cente... More >>r, Minneapolis, Minnesota, 55417, United States Less <<
NCT01896492 PCOS PHASE4 COMPLETED 2025-06-13 -
NCT00396396 Creatinine Clearance UNKNOWN - Eastern Virginia Medical Schoo... More >>l/Nephrology Associates, Norfolk, Virginia, 23507, United States Less <<
NCT02788292 Adipose Tissue Atrophy|Deformi... More >>ty of Reconstructed Breast|Graft Loss Less << PHASE4 WITHDRAWN 2020-11-16 -
NCT05123365 Myeloproliferative Neoplasm|MP... More >>N|Essential Thrombocythemia|Polycythemia Vera|Myelofibrosis Less << PHASE1|PHASE2 RECRUITING 2026-11-15 University of California, Irvi... More >>ne, Irvine, California, 92617, United States|Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange, California, 92868, United States Less <<
NCT05241262 Mitochondrial Disease PHASE1 RECRUITING 2025-04-25 Columbia University Irving Med... More >>ical Center, New York, New York, 10032, United States Less <<
NCT01800526 Sickle Cell Disease|Sickle Cel... More >>l Anemia Less << PHASE1|PHASE2 COMPLETED 2020-06-30 University of Washington, Seat... More >>tle, Washington, 98106, United States Less <<
NCT00542750 Cannabis Dependence PHASE1|PHASE2 COMPLETED 2025-12-08 Medical University of South Ca... More >>rolina, Charleston, South Carolina, 29425, United States Less <<
NCT05081479 Lymphoma PHASE1 RECRUITING 2025-10-21 Memorial Sloan Kettering Baski... More >>ng Ridge (Limited Protocol Activities), Basking Ridge, New Jersey, 07920, United States|Memorial Sloan Kettering Monmouth (Limited Protocol Activities), Middletown, New Jersey, 07748, United States|Memorial Sloan Kettering Bergen (Limited Protocol Activities), Montvale, New Jersey, 07645, United States|Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities), Commack, New York, 11725, United States|Memorial Sloan Kettering Westchester (Limited Protocol Activities), Harrison, New York, 10604, United States|Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States|Memorial Sloan Kettering Nassau (Limited Protocol Activities), Uniondale, New York, 11553, United States Less <<
NCT01424033 Interstitial Lung Disease|Conn... More >>ective Tissue Disease Less << PHASE2|PHASE3 TERMINATED - University of Michigan, Ann Ar... More >>bor, Michigan, 48109, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

6.13mL

1.23mL

0.61mL

30.64mL

6.13mL

3.06mL

61.28mL

12.26mL

6.13mL

Dissolving Methods
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

Historical Records

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