Evidence map›Paper›PMID 37870907›Full record

ArticleDiabetes2024

Liver-Selective Imidazolopyrazine Mitochondrial Uncoupler SHD865 Reverses Adiposity and Glucose Intolerance in Mice.

Martina Beretta, Yumin Dai, Ellen M Olzomer, Calum S Vancuylenburg, José A Santiago-Rivera, Ashleigh M Philp, Stefan R Hargett, Keyong Li, Divya P Shah, Sing-Young Chen and 13 more

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

Article in Diabetes, 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
1.8field-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, 10 citations in OpenAlex.

  1. Article
  2. Mitochondrial control of glycerolipid synthesis by a PEP shuttle.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 2 countries.

Martina BerettaSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales, Australia.
Yumin DaiDepartment of Chemistry and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, VA.
Ellen M OlzomerSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales, Australia.
Calum S VancuylenburgSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales, Australia.
José A Santiago-RiveraDepartment of Chemistry and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, VA.
Ashleigh M PhilpSt Vincent's Clinical School, UNSW Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Stefan R HargettDepartment of Pharmacology, University of Virginia, Charlottesville, VA.
Keyong LiDepartment of Pharmacology, University of Virginia, Charlottesville, VA.
Divya P ShahSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales, Australia.
Sing-Young ChenSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales, Australia.
Stephanie J AlexopoulosSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales, Australia.
Catherine LiSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales, Australia.
Thurl E HarrisDepartment of Pharmacology, University of Virginia, Charlottesville, VA.ORCID 0000-0003-1742-6043
Brendan LeeBiological Resources Imaging Laboratory, University of New South Wales, Sydney, New South Wales, Australia.
Michel WathierLife Biosciences, Boston, MA.
Jennifer M CermakLife Biosciences, Boston, MA.
Simon P TuckerLife Biosciences, Boston, MA.
Nigel TurnerCellular Bioenergetics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
Douglas A BaylissDepartment of Pharmacology, University of Virginia, Charlottesville, VA.
Andrew PhilpCentre for Healthy Ageing, Centenary Institute, Camperdown, New South Wales, Australia.
Frances L ByrneSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales, Australia.
Webster L SantosDepartment of Chemistry and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, VA.ORCID 0000-0002-4731-8548
Kyle L HoehnSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales, Australia.ORCID 0000-0002-0214-3238
UNSW Sydney · AUUniversity of Virginia · USMetLife (United States) · USVirginia Tech · USUniversity of Technology Sydney · AUVictor Chang Cardiac Research Institute · AU

Funding

VT Initiative for Maximizing Student DiversityR25GM072767 · NIGMS · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI SMITH, EDWARD J · 2007 to 2021
$6.9M
Therapeutic Mitochondrial UncouplersR01DK128612 · NIDDK · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI HOEHN, KYLE LEE, SANTOS, WEBSTER L · 2021 to 2024
$2.2M
CSR NIH HHS R01DK128612NIDDK NIH HHS R01 DK128612NIGMS NIH HHS R25 GM072767
6 · The paper itself

Abstract

Excess body fat is a risk factor for metabolic diseases and is a leading preventable cause of morbidity and mortality worldwide. There is a strong need to find new treatments that decrease the burden of obesity and lower the risk of obesity-related comorbidities, including cardiovascular disease and type 2 diabetes. Pharmacologic mitochondrial uncouplers represent a potential treatment for obesity through their ability to increase nutrient oxidation. Herein, we report the in vitro and in vivo characterization of compound SHD865, the first compound to be studied in vivo in a newly discovered class of imidazolopyrazine mitochondrial uncouplers. SHD865 is a derivative of the furazanopyrazine uncoupler BAM15. SHD865 is a milder mitochondrial uncoupler than BAM15 that results in a lower maximal respiration rate. In a mouse model of diet-induced adiposity, 6-week treatment with SHD865 completely restored normal body composition and glucose tolerance to levels like those of chow-fed controls, without altering food intake. SHD865 treatment also corrected liver steatosis and plasma hyperlipidemia to normal levels comparable with chow-fed controls. SHD865 has maximal oral bioavailability in rats and slow clearance in human microsomes and hepatocytes. Collectively, these data identify the potential of imidazolopyrazine mitochondrial uncouplers as drug candidates for the treatment of obesity-related disorders. ARTICLE HIGHLIGHTS:

Indexed as

Diabetes Mellitus, Type 2Glucose IntoleranceAdiposityAnimalsDiet, High-FatHumansLiverMiceMice, Inbred C57BLObesityRats

Identifiers

PMID37870907
PMCPMC10882157
OpenAlexW4387866333

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.