Evidence map›Paper›PMID 42679036›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Design and structural basis of selective nonsteroidal inhibitors of aster cholesterol trafficking.

Hyunsoo Kim, Beatriz Romartinez-Alonso, Xu Xiao, Yajing Gao, John Paul Kennelly, Alessandra Ferrari, Rui Li, Liujuan Cui, Emily Whang, John W R Schwabe and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 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

12 authors.

Hyunsoo Kim *Department of Chemistry, University of California, Los Angeles, CA 90095.
Beatriz Romartinez-Alonso *Department of Molecular and Cell Biology, Institute of Structural and Chemical Biology, University of Leicester, Leicester LE1 7RH, United Kingdom.ORCID 0000-0002-3061-6696
Xu Xiao *Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095.
Yajing GaoDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095.ORCID 0000-0002-8836-4452
John Paul KennellyDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095.ORCID 0000-0002-4399-3976
Alessandra FerrariDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095.
Rui LiDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095.
Liujuan CuiHematology and Oncology, Department of Medicine, University of California, Los Angeles, CA 90095.ORCID 0000-0001-6186-1558
Emily WhangDivision of Pediatric Gastroenterology, Hepatology and Nutrition, University of California, Los Angeles, CA 90095.
John W R SchwabeDepartment of Molecular and Cell Biology, Institute of Structural and Chemical Biology, University of Leicester, Leicester LE1 7RH, United Kingdom.ORCID 0000-0003-2865-4383
Michael E JungDepartment of Chemistry, University of California, Los Angeles, CA 90095.
Peter TontonozDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095.ORCID 0000-0003-1259-0477

Funding

Understanding the Influence of Lipid Homeostasis on T cell FunctionP01HL146358 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FONG, LOREN GI · 2019 to 2023
$11.7M
UCLA Child Health Research Career Development AwardK12HD111040 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Sherin U Devaskar, Shafali Spurling Jeste · 2023 to 2026
$1.2M
Regulation of intestinal lipid metabolism by type-3 immune cytokineK99DK138289 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yajing Gao · 2025 to 2026
$181k
Fondation Leducq (Leducq Foundation) 19CVD04NHLBI NIH HHS P01 HL146358NICHD NIH HHS K12 HD111040NIDDK NIH HHS K99 DK138289
6 · The paper itself

Abstract

Aster proteins (Aster-A, -B, and -C) are crucial for transporting cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER). Asters are expressed in a cell type-specific manner across tissues. Their global disruption leads to varied physiological outcomes given the diverse roles of cholesterol throughout the body. We previously identified sterol analogs, such AI-3d, that inhibit all three Aster proteins. However, their utility is limited by toxicity and off-target effects. Here, we report the development of nonsteroidal Aster inhibitors that are active in cells and in vivo, using binding-guided design to generate compounds with isoform-selective affinities. We found that YKJ-124 is a low-toxicity, Aster-A-preferring inhibitor that elevates PM-accessible cholesterol in primary T cells and potentiates store-operated Ca

Indexed as

CholesterolAnimalsBiological TransportCell MembraneDrug DesignEndoplasmic ReticulumHumansMiceCholesterolcholesterollipid transportsmall molecule inhibitors

Identifiers

PMID42679036
PMCPMC13552655

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.