Evidence map›Paper›PMID 36867738›Full record

ArticleChemistry (Weinheim an der Bergstrasse, Germany)2023

CryoEM Structure with ATP Synthase Enables Late-Stage Diversification of Cruentaren A.

Xiaozheng Dou, Hui Guo, Terin D'Amico, Leah Abdallah, Chitra Subramanian, Bhargav A Patel, Mark Cohen, John L Rubinstein, Brian S J Blagg

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Xiaozheng DouDepartment of Chemistry and Biochemistry, The University of Notre Dame, Notre Dame, IN, 46556, USA.
Hui GuoMolecular Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
Terin D'AmicoDepartment of Chemistry and Biochemistry, The University of Notre Dame, Notre Dame, IN, 46556, USA.
Leah AbdallahDepartment of Surgery, University of Michigan, Ann Arbor, MI, 48109, USA.
Chitra SubramanianDepartments of Surgery and Bioengineering, Carle Illinois College of Medicine, University of Illinois, Urbana-Champaign, IL, 61801, USA.
Bhargav A PatelDepartment of Chemistry and Biochemistry, The University of Notre Dame, Notre Dame, IN, 46556, USA.
Mark CohenDepartments of Surgery and Bioengineering, Carle Illinois College of Medicine, University of Illinois, Urbana-Champaign, IL, 61801, USA.
John L RubinsteinMolecular Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
Brian S J BlaggDepartment of Chemistry and Biochemistry, The University of Notre Dame, Notre Dame, IN, 46556, USA.ORCID http://orcid.org/0000-0002-6200-3480

Funding

Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Optimization and Investigation of Cruentaren A analogsR01CA216919 · NCI · UNIVERSITY OF NOTRE DAME · PI BLAGG, BRIAN S J, COHEN, MARK STEVEN · 2017 to 2021
$1.4M
CSR NIH HHS CA216919NCATS NIH HHS UL1 TR002529NCI NIH HHS R01 CA216919
6 · The paper itself

Abstract

Cruentaren A is a natural product that exhibits potent antiproliferative activity against various cancer cell lines, yet its binding site within ATP synthase remained unknown, thus limiting the development of improved analogues as anticancer agents. Herein, we report the cryogenic electron microscopy (cryoEM) structure of cruentaren A bound to ATP synthase, which allowed the design of new inhibitors through semisynthetic modification. Examples of cruentaren A derivatives include a trans-alkene isomer, which was found to exhibit similar activity to cruentaren A against three cancer cell lines as well as several other analogues that retained potent inhibitory activity. Together, these studies provide a foundation for the generation of cruentaren A derivatives as potential therapeutics for the treatment of cancer.

Indexed as

Antineoplastic AgentsNeoplasmsAdenosine TriphosphateCell LineCryoelectron MicroscopyHumansMacrolidesMolecular StructureStructure-Activity RelationshipAdenosine TriphosphateAntineoplastic Agentscruentaren AMacrolidesATP synthasecruentaren AcryoEM structurelate-stage modificationnatural product

Identifiers

PMID36867738
PMCPMC10205660

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Registered trials

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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.