Evidence map›Paper›PMID 37178691›Full record

ArticleCell chemical biology2023

Identification of structurally diverse FSP1 inhibitors that sensitize cancer cells to ferroptosis.

Joseph M Hendricks, Cody E Doubravsky, Eddie Wehri, Zhipeng Li, Melissa A Roberts, Kirandeep K Deol, Mike Lange, Irene Lasheras-Otero, Jeremiah D Momper, Scott J Dixon and 3 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 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
23.3field-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

85 citing papers in PubMed, 90 citations in OpenAlex.

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  11. CoQExperimental & molecular medicine · 2026
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25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

Joseph M HendricksDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cody E DoubravskyDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Eddie WehriThe Henry Wheeler Center for Emerging and Neglected Diseases, University of California, Berkeley, Berkeley, CA 94720, USA.
Zhipeng LiDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Melissa A RobertsDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Kirandeep K DeolDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Mike LangeDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Irene Lasheras-OteroCancer Signaling Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), 31008 Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.
Jeremiah D MomperSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Scott J DixonDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Kirill BersukerDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Julia SchaletzkyThe Henry Wheeler Center for Emerging and Neglected Diseases, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: jschaletzky@berkeley.edu.
James A OlzmannDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA; Miller Institute for Basic Research in Science, University of California, Berkeley, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub - San Francisco, San Francisco, CA 94158, USA. Electronic address: olzmann@berkeley.edu.
University of California, Berkeley · USMiller College · USStanford University · USUniversidad Publica de Navarra · ESUniversity of California San Diego · US

Funding

Characterizing the Regulation of FerroptosisR01GM122923 · NIGMS · STANFORD UNIVERSITY · PI Scott Dixon · 2017 to 2026
$3.4M
Molecular Mechanisms of Lipid Droplet BiogenesisR01GM112948 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI OLZMANN, JAMES A · 2015 to 2024
$3.1M
NIGMS NIH HHS R01 GM112948NIGMS NIH HHS R01 GM122923
6 · The paper itself

Abstract

Ferroptosis is a regulated form of cell death associated with the iron-dependent accumulation of phospholipid hydroperoxides. Inducing ferroptosis is a promising approach to treat therapy-resistant cancer. Ferroptosis suppressor protein 1 (FSP1) promotes ferroptosis resistance in cancer by generating the antioxidant form of coenzyme Q10 (CoQ). Despite the important role of FSP1, few molecular tools exist that target the CoQ-FSP1 pathway. Through a series of chemical screens, we identify several structurally diverse FSP1 inhibitors. The most potent of these compounds, ferroptosis sensitizer 1 (FSEN1), is an uncompetitive inhibitor that acts selectively through on-target inhibition of FSP1 to sensitize cancer cells to ferroptosis. Furthermore, a synthetic lethality screen reveals that FSEN1 synergizes with endoperoxide-containing ferroptosis inducers, including dihydroartemisinin, to trigger ferroptosis. These results provide new tools that catalyze the exploration of FSP1 as a therapeutic target and highlight the value of combinatorial therapeutic regimes targeting FSP1 and additional ferroptosis defense pathways.

Indexed as

FerroptosisNeoplasmsAntioxidantsCell DeathHumansLipid PeroxidationAntioxidantscancercell deathcoenzyme Q10endoperoxideferroptosisFSP1glutathioneGPX4lipid peroxidationsmall molecule screen

Identifiers

PMID37178691
PMCPMC10524360
OpenAlexW4376275349

What OpenQuestion holds

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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 OpenQuestion graph.