Evidence map›Paper›PMID 27435960›Full record

ArticleeLife2016

Ceapins are a new class of unfolded protein response inhibitors, selectively targeting the ATF6α branch.

Ciara M Gallagher, Carolina Garri, Erica L Cain, Kenny Kean-Hooi Ang, Christopher G Wilson, Steven Chen, Brian R Hearn, Priyadarshini Jaishankar, Andres Aranda-Diaz, Michelle R Arkin and 2 more

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

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed
11.6field-weighted citation impact, top 1% 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

131 citing papers in PubMed, 199 citations in OpenAlex.

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71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Ciara M GallagherDepartment of Biochemistry and Biophysics, Howard Hughes MedicaI Institute, University of California, San Francisco, United States.
Carolina GarriDepartment of Biochemistry and Biophysics, Howard Hughes MedicaI Institute, University of California, San Francisco, United States.
Erica L CainDepartment of Biochemistry and Biophysics, Howard Hughes MedicaI Institute, University of California, San Francisco, United States.
Kenny Kean-Hooi AngSmall Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
Christopher G WilsonSmall Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
Steven ChenSmall Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
Brian R HearnSmall Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
Priyadarshini JaishankarSmall Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
Andres Aranda-DiazDepartment of Biochemistry and Biophysics, Howard Hughes MedicaI Institute, University of California, San Francisco, United States.
Michelle R ArkinSmall Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
Adam R RensloSmall Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
Peter WalterDepartment of Biochemistry and Biophysics, Howard Hughes MedicaI Institute, University of California, San Francisco, United States.ORCID 0000-0002-6849-708X
University of California, San Francisco · USHoward Hughes Medical Institute · US

Funding

Defining the role of proteostasis pathways in cancer drug resistanceF32CA177128 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CAIN, ERICA LYNN · 2013 to 2014
$58k
Howard Hughes Medical InstituteNCI NIH HHS F32 CA177128
6 · The paper itself

Abstract

The membrane-bound transcription factor ATF6α plays a cytoprotective role in the unfolded protein response (UPR), required for cells to survive ER stress. Activation of ATF6α promotes cell survival in cancer models. We used cell-based screens to discover and develop Ceapins, a class of pyrazole amides, that block ATF6α signaling in response to ER stress. Ceapins sensitize cells to ER stress without impacting viability of unstressed cells. Ceapins are highly specific inhibitors of ATF6α signaling, not affecting signaling through the other branches of the UPR, or proteolytic processing of its close homolog ATF6β or SREBP (a cholesterol-regulated transcription factor), both activated by the same proteases. Ceapins are first-in-class inhibitors that can be used to explore both the mechanism of activation of ATF6α and its role in pathological settings. The discovery of Ceapins now enables pharmacological modulation all three UPR branches either singly or in combination.

Indexed as

Activating Transcription Factor 6Cell LineCell SurvivalDrug Evaluation, PreclinicalEnzyme InhibitorsHigh-Throughput Screening AssaysHumansPyrazolesUnfolded Protein ResponseActivating Transcription Factor 6ATF6 protein, humanEnzyme InhibitorsPyrazolesATF6-alphacell biologyendoplasmic reticulumER to Golgi traffickinghumansite-1-proteasesmall molecule screeningunfolded protein response

Identifiers

PMID27435960
PMCPMC4954757
OpenAlexW2495220859

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.