Evidence mapPaperPMID 36947831Full record

ArticleACS chemical biology2023

PROTAC-Mediated Selective Degradation of Cytosolic Soluble Epoxide Hydrolase Enhances ER Stress Reduction.

Yuxin Wang, Christophe Morisseau, Akihiro Takamura, Debin Wan, Dongyang Li, Simone Sidoli, Jun Yang, Dennis W Wolan, Bruce D Hammock, Seiya Kitamura

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. ACS medicinal chemistry letters · 2024
    Article
  4. Soluble epoxide hydrolase-targeting PROTAC activates AMPK and inhibits endoplasmic reticulum stress.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023
    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

10 authors at 3 institutions in 1 country.

Yuxin WangDepartment of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, California 95616, United States.ORCID 0000-0002-0305-9820
Christophe MorisseauDepartment of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, California 95616, United States.
Akihiro TakamuraDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, California 92037, United States.
Debin WanDepartment of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, California 95616, United States.
Dongyang LiDepartment of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, California 95616, United States.ORCID 0000-0002-5603-3608
Simone SidoliDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
Jun YangDepartment of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, California 95616, United States.
Dennis W WolanDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, California 92037, United States.
Bruce D HammockDepartment of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, California 95616, United States.ORCID 0000-0003-1408-8317
Seiya KitamuraDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, California 92037, United States.ORCID 0000-0003-2453-849X
UC Davis Comprehensive Cancer CenterScripps Research Institute · USAlbert Einstein College of Medicine · US

Funding

WORD PROCESSORP30CA013330 · YESHIVA UNIVERSITY · 1985 to 2025
$27.5M
TRANSPORT, TRANSFORMATION &REMEDIATION OF VOCS IN THE VADOSE ZONE &GROUND WATERP42ES004699 · UNIVERSITY OF CALIFORNIA DAVIS · 1987 to 2005
$14.0M
UC Davis CounterACT Center of Excellence: Developing Therapeutic Strategies for Mitigating the Chronic Neurological Consequences of Acute Organophosphate IntoxicationU54NS127758 · UNIVERSITY OF CALIFORNIA AT DAVIS · 2025 to 2025
$3.1M
MIND Institute Intellectual and Developmental Disabilities Research CenterP50HD103526 · UNIVERSITY OF CALIFORNIA AT DAVIS · 2025 to 2025
$1.2M
Bioactive lipids as effectors and indicators of the deleterious effects of environmental exposure on chronic diseasesR35ES030443 · UNIVERSITY OF CALIFORNIA AT DAVIS · 2025 to 2025
$1.0M
NCI NIH HHS P30 CA013330NICHD NIH HHS P50 HD103526NIEHS NIH HHS P42 ES004699NIEHS NIH HHS R35 ES030443NIGMS NIH HHS K99 GM138758NIGMS NIH HHS R00 GM138758NIGMS NIH HHS R35 GM136286NIH HHS S10 OD030286NINDS NIH HHS U54 NS127758
6 · The paper itself

Abstract

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme responsible for lipid metabolism and is a promising drug target. Here, we report the first-in-class PROTAC small-molecule degraders of sEH. Our optimized PROTAC selectively targets the degradation of cytosolic but not peroxisomal sEH, resulting in exquisite spatiotemporal control. Remarkably, our sEH PROTAC molecule has higher potency in cellular assays compared to the parent sEH inhibitor as measured by the significantly reduced ER stress. Interestingly, our mechanistic data indicate that our PROTAC directs the degradation of cytosolic sEH via the lysosome, not through the proteasome. The molecules presented here are useful chemical probes to study the biology of sEH with the potential for therapeutic development. Broadly, our results represent a proof of concept for the superior cellular potency of sEH degradation over sEH enzymatic inhibition, as well as subcellular compartment-selective modulation of a protein by PROTACs.

Indexed as

Endoplasmic Reticulum StressEpoxide HydrolasesProteolysis Targeting ChimeraCytosolEpoxide HydrolasesProteolysis Targeting Chimera

Identifiers

PMID36947831
PMCPMC10586715
OpenAlexW4353044677

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.