Synonym
APAP-Cys, 3-Cysteinylacetaminophen TFA salt, 3-(cysteine-S-yl)acetaminophen; PQN 91930; PQN-91930; PQN91930
IUPAC/Chemical Name
S-[5-(acetylamino)-2-hydroxyphenyl]-L-cysteine, trifluoroacetate salt
InChi Key
PDZGEXMJHANKLR-QRPNPIFTSA-N
InChi Code
InChI=1S/C11H14N2O4S.C2HF3O2/c1-6(14)13-7-2-3-9(15)10(4-7)18-5-8(12)11(16)17;3-2(4,5)1(6)7/h2-4,8,15H,5,12H2,1H3,(H,13,14)(H,16,17);(H,6,7)/t8-;/m0./s1
SMILES Code
OC1=C(SC[C@H](N)C(O)=O)C=C(NC(C)=O)C=C1.OC(C(F)(F)F)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
PQN91930, also known as 3-Cysteinylacetaminophen TFA salt is an acetaminophen-protein adduct formed during the metabolism of acetaminophen.
In vitro activity:
This study examined whether ATP-binding cassette (ABC) transporters play a role in the cellular efflux of APAP, APAP-GSH, and APAP-CYS. The ABC transport proteins P-gp/ABCB1, BSEP/ABCB11, BCRP/ABCG2, and MRP/ABCC1-5 were overexpressed in HEK293 cells and membrane vesicles were produced. Whereas P-gp, BSEP, MRP3, MRP5, and BCRP did not transport any of the compounds, uptake of APAP-GSH was found for MRP1, MRP2 and MRP4. APAP-CYS appeared to be a substrate of MRP4 and none of the ABC proteins transported APAP. The results suggest that the NAPQI metabolite APAP-CYS can be excreted into plasma by MRP4, where it could be a useful biomarker for APAP exposure and toxicity. Characterization of the cellular efflux of APAP-CYS is important for its development as a biomarker, because plasma concentrations might be influenced by drug-transporter interactions and upregulation of MRP4.
Reference: Arch Toxicol. 2020 Sep;94(9):3027-3032. https://pubmed.ncbi.nlm.nih.gov/32472168/
In vivo activity:
Acetaminophen (APAP) nephrotoxicity has been observed both in humans and research animals. Recent investigations have focused on the possible involvement of glutathione-derived APAP metabolites in APAP nephrotoxicity and have demonstrated that administration of acetaminophen-cysteine (APAP-CYS) potentiated APAP-induced renal injury with no effects on APAP-induced liver injury. Additionally, APAP-CYS treatment alone resulted in a dose-responsive renal GSH depletion. This APAP-CYS-induced renal GSH depletion could interfere with intrarenal detoxification of APAP or its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI) and may be the mechanism responsible for the potentiation of APAP nephrotoxicity.
Reference: Toxicol Appl Pharmacol. 2005 Jan 15;202(2):160-71. https://pubmed.ncbi.nlm.nih.gov/15629191/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
0.2 |
0.44 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
384.33
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Koenderink JB, van den Heuvel JJMW, Bilos A, Vredenburg G, Vermeulen NPE, Russel FGM. Human multidrug resistance protein 4 (MRP4) is a cellular efflux transporter for paracetamol glutathione and cysteine conjugates. Arch Toxicol. 2020 Sep;94(9):3027-3032. doi: 10.1007/s00204-020-02793-4. Epub 2020 May 29. PMID: 32472168; PMCID: PMC7415487.
2. Wei M, Gu X, Li H, Zheng Z, Qiu Z, Sheng Y, Lu B, Wang Z, Ji L. EGR1 is crucial for the chlorogenic acid-provided promotion on liver regeneration and repair after APAP-induced liver injury. Cell Biol Toxicol. 2023 Feb 21. doi: 10.1007/s10565-023-09795-9. Epub ahead of print. PMID: 36809385.
3. Stern ST, Bruno MK, Horton RA, Hill DW, Roberts JC, Cohen SD. Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the gamma-glutamyl cycle. Toxicol Appl Pharmacol. 2005 Jan 15;202(2):160-71. doi: 10.1016/j.taap.2004.06.029. PMID: 15629191.
In vitro protocol:
1. Koenderink JB, van den Heuvel JJMW, Bilos A, Vredenburg G, Vermeulen NPE, Russel FGM. Human multidrug resistance protein 4 (MRP4) is a cellular efflux transporter for paracetamol glutathione and cysteine conjugates. Arch Toxicol. 2020 Sep;94(9):3027-3032. doi: 10.1007/s00204-020-02793-4. Epub 2020 May 29. PMID: 32472168; PMCID: PMC7415487.
In vivo protocol:
1. Wei M, Gu X, Li H, Zheng Z, Qiu Z, Sheng Y, Lu B, Wang Z, Ji L. EGR1 is crucial for the chlorogenic acid-provided promotion on liver regeneration and repair after APAP-induced liver injury. Cell Biol Toxicol. 2023 Feb 21. doi: 10.1007/s10565-023-09795-9. Epub ahead of print. PMID: 36809385.
2. Stern ST, Bruno MK, Horton RA, Hill DW, Roberts JC, Cohen SD. Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the gamma-glutamyl cycle. Toxicol Appl Pharmacol. 2005 Jan 15;202(2):160-71. doi: 10.1016/j.taap.2004.06.029. PMID: 15629191.
1. Yoon, E., Babar, A., Choudhary, M., et al. Acetaminophen-induced hepatotoxicity: A comprehensive update. J. Clin. Transl. Hepatol. 4(2), 131-142 (2016).
2. Stern, S.T., Bruno, M.K., Horton, R.A., et al. Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the γ-glutamyl cycle. Toxicol. Appl. Pharmacol. 202(2), 160-171 (2005).
3. Heard, K., Green, J.L., Anderson, V., et al. Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing. Br. J. Clin. Pharmacol. 81(3), 562-568 (2016).
4. O'Malley, G.F., Mizrahi, F., Giraldo, P., et al. Protein-derived acetaminophen-cysteine can be detected after repeated supratherapeutic ingestion of acetaminophen in the absence of hepatotoxicity. J. Med. Toxicol. 11(3), 317-320 (2015).
