Evidence map›Paper›PMID 41796682›Full record

ArticleJournal of lipid research2026

The compound LY295427 antagonizes 25-hydroxycholesterol through binding to INSIG.

Xing-Yan Wen, De-Jie Zhang, Li-Ming He, Ming Sun, Qi Jiang, Ying Zhu, Bao-Liang Song, Wen-Wei Qiu, Xiao-Yi Lu

Abstract read
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Article in Journal of lipid research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

9 authors.

Xing-Yan WenState Key Laboratory of Metabolism and Regulation in Complex Organisms, College of Life Sciences, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
De-Jie ZhangShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.
Li-Ming HeShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.
Ming SunState Key Laboratory of Metabolism and Regulation in Complex Organisms, College of Life Sciences, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
Qi JiangDepartment of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China.
Ying ZhuDepartment of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China.
Bao-Liang SongState Key Laboratory of Metabolism and Regulation in Complex Organisms, College of Life Sciences, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
Wen-Wei QiuShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China. Electronic address: wwqiu@chem.ecnu.edu.cn.
Xiao-Yi LuState Key Laboratory of Metabolism and Regulation in Complex Organisms, College of Life Sciences, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. Electronic address: luxiaoyi@whu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

25-Hydroxycholesterol (25-HC) regulates cholesterol metabolism by inhibiting the maturation of SREBP and promoting the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). The compound LY295427 can reverse 25-HC-mediated suppression of SREBP processing, but the mechanism is unclear. In addition, it is unknown whether LY295427 is able to antagonize the sterol-regulated degradation of HMGCR. In this study, we found that LY295427 prevented the 25-HC-induced interaction between SREBP cleavage-activating protein and INSIG-1 and caused the translocation of SREBP cleavage-activating protein to the Golgi even in the presence of 25-HC. Using a photoreactive LY295427 probe, we demonstrated that it directly bound to INSIG-1, which could be competed off by 25-HC. In addition, LY295427 blocked 25-HC-induced ubiquitination and degradation of HMGCR. Together, this study suggests that LY295427 competes with 25-HC to bind INSIG and therefore blunts 25-HC-induced inhibition of SREBP processing and degradation of HMGCR.

Indexed as

HydroxycholesterolsMembrane ProteinsAnimalsGolgi ApparatusHEK293 CellsHumansHydroxymethylglutaryl CoA ReductasesIntracellular Signaling Peptides and ProteinsProtein Binding25-hydroxycholesterolHydroxycholesterolsHydroxymethylglutaryl CoA ReductasesINSIG1 protein, humanIntracellular Signaling Peptides and ProteinsMembrane ProteinsSREBP cleavage-activating protein25-HCcholesterolHMGCRINSIGLY295427

Identifiers

PMID41796682
PMCPMC13090600

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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.