Evidence map›Paper›PMID 41208336›Full record

ArticleJournal of medicinal chemistry2025

Potent Preorganized Pyrazolidine Cyclophilin D Inhibitors Prevent Mitochondrial and Organ Injury in a Mouse Pancreatitis Disease Model.

Muhammad Awais, Christopher M Woodley, Liqun Guo, Michael Rogers, Neil Kershaw, Thomas Zacharchenko, Emma Shore, Arjun Kattakayam, Rajarshi Mukherjee, David N Criddle and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

19 authors.

Muhammad AwaisDepartment of Molecular and Clinical Cancer Medicine, Liverpool Pancreatitis Research Group, University of Liverpool, Liverpool L69 7BE, U.K.
Christopher M WoodleyRobert Robinson Laboratories, University of Liverpool, Chemistry, Oxford Street, Liverpool L69 7ZD, U.K.
Liqun GuoRobert Robinson Laboratories, University of Liverpool, Chemistry, Oxford Street, Liverpool L69 7ZD, U.K.
Michael RogersRobert Robinson Laboratories, University of Liverpool, Chemistry, Oxford Street, Liverpool L69 7ZD, U.K.
Neil KershawRobert Robinson Laboratories, University of Liverpool, Chemistry, Oxford Street, Liverpool L69 7ZD, U.K.
Thomas ZacharchenkoWellcome Centre for Cell-Matrix Research, The University of Manchester, Michael Smith Building Dover Street, Manchester M13 9PT, U.K.
Emma ShoreRobert Robinson Laboratories, University of Liverpool, Chemistry, Oxford Street, Liverpool L69 7ZD, U.K.
Arjun KattakayamDepartment of Molecular and Clinical Cancer Medicine, Liverpool Pancreatitis Research Group, University of Liverpool, Liverpool L69 7BE, U.K.
Rajarshi MukherjeeDepartment of Molecular and Clinical Cancer Medicine, Liverpool Pancreatitis Research Group, University of Liverpool, Liverpool L69 7BE, U.K.
David N CriddleDepartment of Molecular and Clinical Cancer Medicine, Liverpool Pancreatitis Research Group, University of Liverpool, Liverpool L69 7BE, U.K.
Suet C LeungRobert Robinson Laboratories, University of Liverpool, Chemistry, Oxford Street, Liverpool L69 7ZD, U.K.
Heather LeeRobert Robinson Laboratories, University of Liverpool, Chemistry, Oxford Street, Liverpool L69 7ZD, U.K.
Joshua Burgess-McCannRobert Robinson Laboratories, University of Liverpool, Chemistry, Oxford Street, Liverpool L69 7ZD, U.K.
Konstantin LuzyaninRobert Robinson Laboratories, University of Liverpool, Chemistry, Oxford Street, Liverpool L69 7ZD, U.K.
Neil G BerryRobert Robinson Laboratories, University of Liverpool, Chemistry, Oxford Street, Liverpool L69 7ZD, U.K.
Svetlana AntonyukDepartment of Molecular and Clinical Cancer Medicine, Liverpool Pancreatitis Research Group, University of Liverpool, Liverpool L69 7BE, U.K.
Lu-Yun LianDepartment of Molecular and Clinical Cancer Medicine, Liverpool Pancreatitis Research Group, University of Liverpool, Liverpool L69 7BE, U.K.ORCID 0000-0001-9481-749X
Robert SuttonDepartment of Molecular and Clinical Cancer Medicine, Liverpool Pancreatitis Research Group, University of Liverpool, Liverpool L69 7BE, U.K.
Paul M O'NeillRobert Robinson Laboratories, University of Liverpool, Chemistry, Oxford Street, Liverpool L69 7ZD, U.K.ORCID 0000-0003-4338-0317

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cyclophilin D inhibitors that prevent opening of the mitochondrial permeability transition pore (MPTP) are potential treatments for a range of acute and chronic diseases, including acute pancreatitis. Here, we report that replacement of carbon with nitrogen in the pyrrolidine headgroup of a series of cyclophilin D inhibitors gives a dramatic enhancement in binding affinity (>40 fold), and prolyl isomerase inhibition (PPIase) activity (>200 fold), which is ascribed to a preorganization of the pyrazolidine amide headgroup. Protein-ligand X-ray crystal structures and NMR and molecular modeling demonstrate the importance of

Indexed as

CyclophilinsMitochondriaPancreatitisPyrazolesAnimalsDisease Models, AnimalHumansMiceMice, Inbred C57BLMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreModels, MolecularPeptidyl-Prolyl Isomerase FStructure-Activity RelationshipCyclophilinsMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PorePeptidyl-Prolyl Isomerase FPyrazoles

Identifiers

PMID41208336
PMCPMC12670411

What Socratic holds

Textmetadata
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 Socratic graph.