Evidence map›Paper›PMID 41982731›Full record

ArticleACS medicinal chemistry letters2026

Dissecting Polypharmacology in Phenotypic Screening to Resolve Ferroptotic and Necrotic Cell-Death Mechanisms.

Kenichi Shimada, Elisabet Gregori-Puigjane, Michael E Stokes, Rachid Skouta, Brent R Stockwell

Abstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2026. 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

5 authors.

Kenichi ShimadaDepartment of Biological Sciences, Columbia University, New York, New York 10027, United States.
Elisabet Gregori-PuigjaneDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, United States.
Michael E StokesDepartment of Biological Sciences, Columbia University, New York, New York 10027, United States.
Rachid SkoutaDepartments of Biology and Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, United States.
Brent R StockwellDepartment of Biological Sciences, Columbia University, New York, New York 10027, United States.ORCID https://orcid.org/0000-0002-3532-3868

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Small molecules frequently induce heterogeneous cell-death programs, complicating the mechanistic interpretation and optimization. Here, we investigate the ferroptotic and necrotic activities of the lethal small molecule CIL56 and related analogs. Although structurally similar, these compounds induce chemically separable death phenotypes. A phenotypic suppressor screen further identified distinct sets of small molecules that selectively attenuate ferroptotic or necrotic death. Classification of suppressor compounds based on shared ligand-based target predictions suggested nonoverlapping groups of candidate protein targets linked to each death modality. Together, these results show that integrating phenotypic screening with suppressor classification and target prediction can improve the interpretability of small-molecule phenotypic screens by prioritizing candidate proteins and pathways underlying the observed biological response.

Indexed as

chemical annotationferroptosisnonapoptotic cell deathphenotypic cell-based screeningpolypharmacologysimilarity ensemble approach

Identifiers

PMID41982731
PMCPMC13071664

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.