Evidence map›Paper›PMID 38312223›Full record

ArticlePNAS nexus2024

Monitoring drug metabolic pathways through extracellular vesicles in mouse plasma.

Xiaofeng Wu, Menchus Quan, Marco Hadisurya, Jianzhong Hu, Yi-Kai Liu, Yuxin Zhuang, Li Li, Anton B Iliuk, Jun J Yang, Shihuan Kuang and 1 more

Open access · goldAbstract read
In one paragraph

Article in PNAS nexus, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
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 3 institutions in 1 country.

Xiaofeng WuDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.ORCID https://orcid.org/0000-0002-8961-2163
Menchus QuanDepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.ORCID https://orcid.org/0000-0002-6656-2036
Marco HadisuryaDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.ORCID https://orcid.org/0000-0002-4453-5854
Jianzhong HuDepartment of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, USA.ORCID https://orcid.org/0000-0002-7548-5802
Yi-Kai LiuDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.ORCID https://orcid.org/0000-0001-8712-3326
Yuxin ZhuangDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
Li LiTymora Analytical Operations, West Lafayette, IN 47906, USA.
Anton B IliukDepartment of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.ORCID https://orcid.org/0000-0002-2914-1363
Jun J YangDepartment of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, USA.ORCID https://orcid.org/0000-0002-4233-3220
Shihuan KuangDepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.ORCID https://orcid.org/0000-0001-9180-3180
W Andy TaoDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.ORCID https://orcid.org/0000-0002-5535-5517
Purdue University West Lafayette · USSt. Jude Children's Research Hospital · USTymora Analytical Operations (United States) · US

Funding

Metabolic regulation of muscle satellite cell homeostasisR01DK132819 · NIDDK · PURDUE UNIVERSITY · PI Shihuan Kuang · 2023 to 2026
$2.0M
Dissecting signaling pathways and seeking EV phosphoproteins as novel biomarkers for Alzheimer's DiseaseRF1AG064250 · NIA · PURDUE UNIVERSITY · PI TAO, W. ANDY · 2020 to 2021
$1.7M
NIA NIH HHS RF1 AG064250NIDDK NIH HHS R01 DK132819
6 · The paper itself

Abstract

The ability to monitor the response of metabolic enzymes to drug exposure in individuals is highly appealing and critical to personalized medicine. Although pharmacogenomics assesses genotypic differences, it does not report changes in metabolic enzyme activities due to environmental factors such as drug interactions. Here, we report a quantitative proteomics strategy to monitor drug metabolic pathways by profiling metabolic enzymes in circulating extracellular vesicles (EVs) upon drug exposure. Mass spectrometry (MS)-based measurement revealed that changes in metabolic enzyme abundance in EVs paralleled those in hepatic cells isolated from liver tissue. Coupling with multiplexed isotopic labeling, we temporally quantified 34 proteins involved in drug absorption, distribution, metabolism, and excretion (ADME) pathways. Out of 44 known ADME proteins in plasma EVs, previously annotated mouse cytochrome P450 3A11 (Cyp3a11), homolog to human CYP3A4, and uridine 5'-diphospho (UDP) glucuronosyltransferase 2A3 (Ugt2a3), increased upon daily rifampicin dosage. Dasatinib, a tyrosine kinase inhibitor to treat leukemia, also elevated Cyp3a11 levels in plasma EVs, but to a lesser extent. Altogether, this study demonstrates that measuring drug enzymes in circulating EVs as an effective surrogate is highly feasible and may transform today's drug discovery and development for personalized medicine.

Indexed as

drug ADMEextracellular vesiclesmass spectrometryP450 enzymesproteomics

Identifiers

PMID38312223
PMCPMC10833468
OpenAlexW4391126692

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.