Evidence map›Paper›PMID 36513726›Full record

ArticleScientific reports2022

A novel small molecule inhibitor of human Drp1.

Ayeshah A Rosdah, Belinda M Abbott, Christopher G Langendorf, Yali Deng, Jia Q Truong, Helen M M Waddell, Naomi X Y Ling, William J Smiles, Lea M D Delbridge, Guei-Sheung Liu and 3 more

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

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.8field-weighted citation impact, top 5% 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

33 citing papers in PubMed, 51 citations in OpenAlex.

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  15. DRP1, fission and apoptosis.Cell death discovery · 2025
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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

13 authors at 6 institutions in 3 countries.

Ayeshah A RosdahSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Belinda M AbbottDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia.
Christopher G LangendorfSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Yali DengSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Jia Q TruongSchool of Science, RMIT University, GPO Box 2476, Melbourne, VIC, 3001, Australia.
Helen M M WaddellDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Naomi X Y LingSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
William J SmilesSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Lea M D DelbridgeDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Guei-Sheung LiuDepartment of Surgery and Medicine, University of Melbourne, Melbourne, VIC, Australia.
Jonathan S OakhillSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Shiang Y LimSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Jessica K HolienSt Vincent's Institute of Medical Research, Fitzroy, VIC, Australia. jessica.holien@rmit.edu.au.
University of Melbourne · AUSt Vincents Institute of Medical Research · AULa Trobe University · AUMonash University · AURMIT University · AUSriwijaya University · ID

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mitochondrial dynamin-related protein 1 (Drp1) is a large GTPase regulator of mitochondrial dynamics and is known to play an important role in numerous pathophysiological processes. Despite being the most widely used Drp1 inhibitor, the specificity of Mdivi-1 towards human Drp1 has not been definitively proven and there have been numerous issues reported with its use including off-target effects. In our hands Mdivi-1 showed varying binding affinities toward human Drp1, potentially impacted by compound aggregation. Herein, we sought to identify a novel small molecule inhibitor of Drp1. From an initial virtual screening, we identified DRP1i27 as a compound which directly bound to the human isoform 3 of Drp1 via surface plasmon resonance and microscale thermophoresis. Importantly, DRP1i27 was found to have a dose-dependent increase in the cellular networks of fused mitochondria but had no effect in Drp1 knock-out cells. Further analogues of this compound were identified and screened, though none displayed greater affinity to human Drp1 isoform 3 than DRP1i27. To date, this is the first small molecule inhibitor shown to directly bind to human Drp1.

Indexed as

DynaminsQuinazolinonesGTP PhosphohydrolasesHumansMitochondrial Dynamics3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinoneDNM1L protein, humanDynaminsGTP PhosphohydrolasesQuinazolinones

Identifiers

PMID36513726
PMCPMC9747717
OpenAlexW4311316949

What OpenQuestion holds

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LicenceCC BY
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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.