Evidence map›Paper›PMID 37918853›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2024

High-Dose Acetaminophen with Concurrent CYP2E1 Inhibition Has Profound Anticancer Activity without Liver Toxicity.

Allyn Bryan, Pavani Pingali, Anthony Faber, Joseph Landry, Jephte Y Akakpo, Hartmut Jaeschke, Howard Li, Won Sok Lee, Lauren May, Bhaumik Patel and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.0field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Can Acetaminophen be Used as a Chemotherapeutic Agent in the Kidney?Journal of biochemical and molecular toxicology · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Allyn BryanDepartment of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.).
Pavani PingaliDepartment of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.).
Anthony FaberDepartment of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.).
Joseph LandryDepartment of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.).
Jephte Y AkakpoDepartment of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.).
Hartmut JaeschkeDepartment of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.).ORCID https://orcid.org/0000-0002-8695-6980
Howard LiDepartment of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.).
Won Sok LeeDepartment of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.).
Lauren MayDepartment of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.).
Bhaumik PatelDepartment of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.).
Alex NeuweltDepartment of Veterans Affairs, Richmond, Virginia. (A.B., P.P., W.S.L., B.P., A.N.); Departments of Oral and Craniofacial Molecular Biology (A.F.) and Human and Molecular Genetics (J.L., L.M.), Virginia Commonwealth University, Richmond, Virginia; Department of Veterans Affairs, Charleston, South Carolina (H.L.); and Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas, Lawrence, Kansas (J.Y.A., H.J.) alexander.neuwelt@va.gov.
Virginia Commonwealth University · US

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Kim Felder Rhoads · 1985 to 2026
$51.0M
Pilot Grants ProgramP30GM118247 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI WEINMAN, STEVEN A · 2016 to 2020
$5.5M
NRSA Training CoreTL1TR002368 · NCATS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Jennifer Lynn Goldman, NICOLE L NOLLEN · 2017 to 2026
$4.0M
Minimizing Fall-Related Injury in Older Adults: a motor learning approachR21AG073892 · NIA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI SOSNOFF, JACOB J. · 2021 to 2022
$429k
High dose acetaminophen with n-acetylcysteine rescue as a novel STAT3 inhibitor with anti-cancer stem cell propertiesIK2BX004914 · VA · VA VETERANS ADMINISTRATION HOSPITAL · PI Alexander Neuwelt · 2022 to 2026
–
BLRD VA IK2 BX004914NCATS NIH HHS TL1 TR002368NCI NIH HHS P30 CA016059NIA NIH HHS R21 AG073892NIGMS NIH HHS P30 GM118247
6 · The paper itself

Abstract

Acetaminophen (AAP) is metabolized by a variety of pathways such as sulfation, glucuronidation, and fatty acid amide hydrolase-mediated conversion to the active analgesic metabolite AM404. CYP2E1-mediated metabolism to the hepatotoxic reactive metabolite NAPQI (N-acetyl-p-benzoquinone imine) is a minor metabolic pathway that has not been linked to AAP therapeutic benefits yet clearly leads to AAP liver toxicity. N-acetylcysteine (NAC) (an antioxidant) and fomepizole (a CYP2E1 inhibitor) are clinically used for the treatment of AAP toxicity. Mice treated with AAP in combination with fomepizole (plus or minus NAC) were assessed for liver toxicity by histology and serum chemistry. The anticancer activity of AAP with NAC and fomepizole rescue was assessed in vitro and in vivo. Fomepizole with or without NAC completely prevented AAP-induced liver toxicity. In vivo, high-dose AAP with NAC/fomepizole rescue had profound antitumor activity against commonly used 4T1 breast tumor and lewis lung carcinoma lung tumor models, and no liver toxicity was detected. The antitumor efficacy was reduced in immune-compromised NOD-scid IL2Rgamma

Indexed as

AcetaminophenCytochrome P-450 CYP2E1AcetylcysteineAnimalsFomepizoleLiverMiceMice, Inbred NODAcetaminophenAcetylcysteineCytochrome P-450 CYP2E1Fomepizole

Identifiers

PMID37918853
PMCPMC10765416
OpenAlexW4388211838

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.