Evidence map›Paper›PMID 37820725›Full record

ArticleCell chemical biology2023

In vivo bioluminescence imaging of labile iron in xenograft models and liver using FeAL-1, an iron-activatable form of D-luciferin.

Ryan L Gonciarz, Honglin Jiang, Linh Tram, Cedric L Hugelshofer, Oscar Ekpenyong, Ian Knemeyer, Allegra T Aron, Christopher J Chang, John A Flygare, Eric A Collisson and 1 more

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

Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 22% 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. A tandem activity-based sensing and labeling strategy reveals antioxidant response element regulation of labile iron pools.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  4. 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

11 authors at 4 institutions in 1 country.

Ryan L GonciarzDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Honglin JiangHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Linh TramDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Cedric L HugelshoferDepartment of Discovery Chemistry, Merck & Co, Inc., South San Francisco, CA 94080, USA.
Oscar EkpenyongADME & Discovery Toxicology, Merck & Co, Inc., South San Francisco, CA 94080, USA.
Ian KnemeyerADME & Discovery Toxicology, Merck & Co, Inc., South San Francisco, CA 94080, USA.
Allegra T AronDepartment of Chemistry and Biochemistry, University of Denver, Denver, CO 80208, USA.
Christopher J ChangDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
John A FlygareDepartment of Discovery Chemistry, Merck & Co, Inc., South San Francisco, CA 94080, USA.
Eric A CollissonHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Adam R RensloDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: adam.renslo@ucsf.edu.
University of California, San Francisco · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USUniversity of California, Berkeley · USUniversity of Denver · US

Funding

Molecular Imaging Probes To Study Redox BiologyR01GM079465 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Christopher J. Chang · 2006 to 2026
$7.8M
Chemical Methods for Ferrous Iron Dependent Drug DeliveryR01AI105106 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RENSLO, ADAM R · 2013 to 2022
$4.6M
Understanding Efficacy and Fe(II)-Promoted Activation of 1,2,4-Trioxolanes in CancerR01CA260860 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLISSON, ERIC, RENSLO, ADAM R · 2021 to 2025
$3.1M
Research Training in Chemistry and Chemical BiologyT32GM145460 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jason E Gestwicki · 2022 to 2026
$3.1M
NCI NIH HHS R01 CA260860NIAID NIH HHS R01 AI105106NIGMS NIH HHS R01 GM079465NIGMS NIH HHS T32 GM145460
6 · The paper itself

Abstract

Dysregulated iron homeostasis underlies diverse pathologies, from ischemia-reperfusion injury to epithelial-mesenchymal transition and drug-tolerant "persister" cancer cell states. Here, we introduce ferrous iron-activatable luciferin-1 (FeAL-1), a small-molecule probe for bioluminescent imaging of the labile iron pool (LIP) in luciferase-expressing cells and animals. We find that FeAL-1 detects LIP fluctuations in cells after iron supplementation, depletion, or treatment with hepcidin, the master regulator of systemic iron in mammalian physiology. Utilizing FeAL-1 and a dual-luciferase reporter system, we quantify LIP in mouse liver and three different orthotopic pancreatic ductal adenocarcinoma tumors. We observed up to a 10-fold increase in FeAL-1 bioluminescent signal in xenograft tumors as compared to healthy liver, the major organ of iron storage in mammals. Treating mice with hepcidin further elevated hepatic LIP, as predicted. These studies reveal a therapeutic index between tumoral and hepatic LIP and suggest an approach to sensitize tumors toward LIP-activated therapeutics.

Indexed as

IronNeoplasmsAnimalsBenzothiazolesHepcidinsHeterograftsHumansLiverLuciferasesLuciferinsMammalsMiceBenzothiazolesD-luciferinHepcidinsIronLuciferasesLuciferinsbioluminescence imagingchemical probesferroptosispancreatic ductal adenocarcinoma

Identifiers

PMID37820725
PMCPMC10841594
OpenAlexW4387503157

What OpenQuestion 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 OpenQuestion graph.