Evidence map›Paper›PMID 36356534›Full record

ArticleBioorganic & medicinal chemistry2022

Bis-aryl-α,β-unsaturated ketone (ABK) chaperonin inhibitors exhibit selective cytotoxicity to colorectal cancer cells that correlates with levels of aberrant HSP60 in the cytosol.

Siddhi Chitre, Anne-Marie Ray, Mckayla Stevens, Emma H Doud, Hope Liechty, Alex Washburn, Katelyn Tepper, Jared Sivinski, Heather M O'Hagan, Millie M Georgiadis and 2 more

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry, 2022. 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
0.7field-weighted citation impact, top 33% 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, 8 citations in OpenAlex.

  1. Chaperonin in health and disease.Molecular biomedicine · 2026
    Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Molecular Chaperonin HSP60: Current Understanding and Future Prospects.International journal of molecular sciences · 2024
    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

12 authors at 3 institutions in 1 country.

Siddhi ChitreIndiana University School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, United States.
Anne-Marie RayIndiana University School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, United States.
Mckayla StevensIndiana University School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, United States.
Emma H DoudIndiana University School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, United States.
Hope LiechtyIndiana University School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, United States.
Alex WashburnIndiana University School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, United States.
Katelyn TepperIndiana University School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, United States.
Jared SivinskiThe University of Arizona, College of Pharmacy, Department of Pharmacology and Toxicology, 1703 E. Mabel St., PO Box 210207, Tucson, AZ 85721, United States.
Heather M O'HaganIndiana University School of Medicine, Medical Sciences Program and Department of Medical and Molecular Genetics, 1001 East 3rd St., Bloomington, IN 47405, United States.
Millie M GeorgiadisIndiana University School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, United States.
Eli ChapmanThe University of Arizona, College of Pharmacy, Department of Pharmacology and Toxicology, 1703 E. Mabel St., PO Box 210207, Tucson, AZ 85721, United States.
Steven M JohnsonIndiana University School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, United States. Electronic address: johnstm@iu.edu.
Indiana University School of MedicineUniversity of Arizona · USIndiana University Bloomington · US

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI David W Clapp · 1999 to 2026
$59.3M
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
Project-005U54DK106846 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Reuben Kapur, Karen Elizabeth Pollok · 2015 to 2026
$9.7M
Selective modulation of bacterial chaperonins by targeting novel small molecule binding sitesR01GM120350 · NIGMS · INDIANA UNIVERSITY INDIANAPOLIS · PI JOHNSON, STEVEN MICHAEL · 2017 to 2021
$2.3M
BD FACSAria SystemS10OD012270 · OD · INDIANA UNIVERSITY INDIANAPOLIS · PI SROUR, EDWARD F · 2013 to 2013
$516k
NCATS NIH HHS UL1 TR002529NCI NIH HHS P30 CA082709NIDDK NIH HHS U54 DK106846NIGMS NIH HHS R01 GM120350NIH HHS S10 OD012270
6 · The paper itself

Abstract

While many studies have established the importance of protein homeostasis in tumor progression, little effort has been made to examine the therapeutic potential of targeting the HSP60 chaperonin system. In healthy cells, HSP60 is localized to the mitochondrial matrix; however, emerging evidence indicates HSP60 can be over-expressed and mis-localized to the cytosol of cancer cells, which is hypothesized to promote tumor cell survival and proliferation. This opens a potential avenue to selectively target the aberrant HSP60 in the cytosol as a chemotherapeutic strategy. In the present work, we examined a series of bis-aryl-α,β-unsaturated ketone (ABK) HSP60 inhibitors for their ability to selectively target cancerous vs non-cancerous colon and intestine cells. We found that lead analogs inhibited migration and clonogenicity of cancer cells, with cytotoxicity correlating with the level of aberrant HSP60 in the cytosol.

Indexed as

ChaperoninsColorectal NeoplasmsChaperonin 10Chaperonin 60CytosolHumansMitochondriaChaperonin 10Chaperonin 60ChaperoninsChaperoninChemotherapeuticsColorectal cancerHsp10HSP60HSPD1Molecular chaperoneProteostasisSmall molecule inhibitors

Identifiers

PMID36356534
PMCPMC11813185
OpenAlexW4307908388

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.