Evidence map›Paper›PMID 42657783›Full record

ArticleeLife2026

A whole-animal phenotypic drug screen identifies suppressors of atherogenic lipoproteins.

Daniel J Kelpsch, Liyun Zhang, James H Thierer, Adrian G Rivera Cruz, Kobe Koren, Urmi Kumar, Yuki Lin, Monica R Hensley, Mira Sohn, Jun O Liu and 3 more

Abstract read
In one paragraph

Article in eLife, 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

5 · Who and what money

Authors and funding

13 authors.

Daniel J KelpschDepartment of Biology, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0000-0002-7383-5530
Liyun ZhangDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0000-0003-3306-0459
James H ThiererDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0000-0002-1679-2255
Adrian G Rivera CruzDepartment of Biology, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0009-0004-3742-1965
Kobe KorenDepartment of Biology, Johns Hopkins University, Baltimore, United States.
Urmi KumarDepartment of Biology, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0009-0004-8942-8237
Yuki LinDepartment of Biology, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0009-0005-7814-9889
Monica R HensleyDepartment of Biology, Johns Hopkins University, Baltimore, United States.
Mira SohnDepartment of Biology, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0009-0000-1929-9856
Jun O LiuDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0000-0003-3842-9841
Thomas LectkaDepartment of Chemistry, Johns Hopkins University, Baltimore, United States.
Jeff S MummDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0000-0002-2575-287X
Steven A FarberDepartment of Biology, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0000-0002-8037-7312

Funding

In vivo HTS assay for novel modulators of Apolipoprotien BR01DK116079 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI FARBER, STEVEN A · 2018 to 2022
$3.2M
A whole-animal small molecule screen to identify and characterize modifiers of Apolipoprotein BF32DK126297 · NIDDK · CARNEGIE INSTITUTION OF WASHINGTON, D.C. · PI KELPSCH, DANIEL · 2020 to 2022
$201k
NIDDK NIH HHS F32 DK126297NIDDK NIH HHS F32DK126297NIDDK NIH HHS R01 DK116079NIDDK NIH HHS R01DK116079
6 · The paper itself

Abstract

Lipoproteins are essential for lipid transport in all bilaterians. A single Apolipoprotein B (ApoB) molecule is the inseparable structural scaffold of each ApoB-containing lipoprotein (B-lps), which are responsible for transporting lipids to peripheral tissues. The cellular mechanisms that regulate ApoB and B-lp production, secretion, transport, and degradation remain to be fully defined. In humans, elevated levels of vascular B-lps play a causative role in cardiovascular disease. Previously, we have detailed that human B-lp biology is remarkably conserved in the zebrafish using an in vivo chemiluminescent reporter of ApoB (LipoGlo) that does not disrupt ApoB function. Thus, the LipoGlo model is an ideal system for identifying novel mechanisms of ApoB modulation and, due to the ability of zebrafish to generate many progeny, is particularly amenable to large-scale phenotypic drug screening. Here, we report a screen of roughly 3000 compounds that identified 49 unique ApoB-lowering hits. Nineteen hits passed orthogonal screening criteria, and seven were subjected to extensive phenotyping. A licorice root component, enoxolone, significantly lowered B-lps only in animals that express a functional allele of the nuclear hormone receptor Hepatocyte Nuclear Factor 4⍺ (HNF4⍺). Consistent with this result, inhibitors of HNF4⍺ also reduce B-lp levels. These data demonstrate that mechanism(s) of action can be rapidly determined from a whole-animal zebrafish phenotypic screen. Given the well-documented role of HNF4⍺ in human B-lp biology, these data validate the LipoGlo screening platform for identifying small-molecule modulators of B-lps that play a critical role in a leading cause of worldwide mortality.

Indexed as

Apolipoproteins BAtherosclerosisLipoproteinsAnimalsDrug Evaluation, PreclinicalHepatocyte Nuclear Factor 4HumansPhenotypeZebrafishApolipoproteins BHepatocyte Nuclear Factor 4Lipoproteinsapolipoprotein Bbiochemistrychemical biologydrug repurposingenoxoloneHNF4phenotypic drug screeningzebrafish

Identifiers

PMID42657783
PMCPMC13521566

What OpenQuestion holds

Textmetadata
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.