Evidence map›Paper›PMID 35095511›Full record

ArticleFrontiers in pharmacology2021

Discovery of Novel Reductive Elimination Pathway for 10-Hydroxywarfarin.

Dakota L Pouncey, Dustyn A Barnette, Riley W Sinnott, Sarah J Phillips, Noah R Flynn, Howard P Hendrickson, S Joshua Swamidass, Grover P Miller

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 55% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. 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

8 authors at 2 institutions in 1 country.

Dakota L PounceyDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Dustyn A BarnetteDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Riley W SinnottDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Sarah J PhillipsDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Noah R FlynnDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States.
Howard P HendricksonDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
S Joshua SwamidassDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States.
Grover P MillerDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
University of Arkansas for Medical Sciences · USWashington University in St. Louis · US

Funding

Systematic Discovery of Bioactivation-Associated Structural AlertsR01GM140635 · NIGMS · WASHINGTON UNIVERSITY · PI MILLER, GROVER P, SWAMIDASS, SANJAY JOSHUA · 2020 to 2023
$1.5M
NIGMS NIH HHS R01 GM140635
6 · The paper itself

Abstract

Coumadin (R/S-warfarin) anticoagulant therapy is highly efficacious in preventing the formation of blood clots; however, significant inter-individual variations in response risks over or under dosing resulting in adverse bleeding events or ineffective therapy, respectively. Levels of pharmacologically active forms of the drug and metabolites depend on a diversity of metabolic pathways. Cytochromes P450 play a major role in oxidizing R- and S-warfarin to 6-, 7-, 8-, 10-, and 4'-hydroxywarfarin, and warfarin alcohols form through a minor metabolic pathway involving reduction at the C11 position. We hypothesized that due to structural similarities with warfarin, hydroxywarfarins undergo reduction, possibly impacting their pharmacological activity and elimination. We modeled reduction reactions and carried out experimental steady-state reactions with human liver cytosol for conversion of

Indexed as

AKR1C3anticoagulationCBR1hydroxywarfarinmetabolismmodelingreductionwarfarin

Identifiers

PMID35095511
PMCPMC8793337
OpenAlexW4205695594

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.