Evidence map›Paper›PMID 30123067›Full record

ArticleInternational journal of biological sciences2018

Astemizole Inhibits mTOR Signaling and Angiogenesis by Blocking Cholesterol Trafficking.

Junfang Lyu, Eun Ju Yang, Sarah A Head, Nana Ai, Baoyuan Zhang, Changjie Wu, Ruo-Jing Li, Yifan Liu, Harapriya Chakravarty, Shaolin Zhang and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of biological sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Upregulation of NPC1 and its association with poor prognosis in gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Article
  4. Review
  5. Severe neurometabolic phenotype inFrontiers in molecular neuroscience · 2023
    Article
  6. Article
  7. The hEag1 KInternational journal of molecular sciences · 2022
    Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Frontiers in pharmacology · 2022
    Article
  14. Article
  15. Review
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

16 authors at 4 institutions in 4 countries.

Junfang LyuFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Eun Ju YangFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Sarah A HeadDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; The SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Nana AiFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Baoyuan ZhangFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Changjie WuFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Ruo-Jing LiDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; The SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Yifan LiuFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Harapriya ChakravartyFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Shaolin ZhangFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Kin Yip TamFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Yongjun DangKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Ho Jeong KwonChemical Genomics Global Research Laboratory, Department of Biotechnology, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
Wei GeFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Jun O LiuDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; The SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Joong Sup ShimFaculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
University of Macau · MOJohns Hopkins University · USFudan University · CNYonsei University · KR

Funding

Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Studies of the Antifungal Drug Itraconazole As A Novel Inhibitor of AngiogenesisR01CA184103 · NCI · JOHNS HOPKINS UNIVERSITY · PI LIU, JUN O. · 2015 to 2019
$1.8M
NCATS NIH HHS UL1 TR001079NCI NIH HHS R01 CA184103
6 · The paper itself

Abstract

Cholesterol plays a key role in membrane protein function and signaling in endothelial cells. Thus, disturbing cholesterol trafficking is an effective approach for inhibiting angiogenesis. We recently identified astemizole (AST), an antihistamine drug, as a cholesterol trafficking inhibitor from a phenotypic screen. In this study, we found that AST induced cholesterol accumulation in the lysosome by binding to the sterol-sensing domain of Niemann-Pick disease, type C1 (NPC1), a lysosomal surface protein responsible for cholesterol transport. Inhibition of cholesterol trafficking by AST led to the depletion of membrane cholesterol, causing SREBP1 nuclear localization. The depletion of membrane cholesterol resulted in dissociation of mammalian target of rapamycin (mTOR) from the lysosomal surface and inactivation of mTOR signaling. These effects were effectively rescued by addition of exogenous cholesterol. AST inhibited endothelial cell proliferation, migration and tube formation in a cholesterol-dependent manner. Furthermore, AST inhibited zebrafish angiogenesis in a cholesterol-dependent manner. Together, our data suggest that AST is a new class of NPC1 antagonist that inhibits cholesterol trafficking in endothelial cells and angiogenesis.

Indexed as

A549 CellsAstemizoleBiological TransportBlotting, WesternCell MovementCell ProliferationCholesterolFluorescent Antibody TechniqueHumansHuman Umbilical Vein Endothelial CellsNeovascularization, PathologicNiemann-Pick C1 ProteinSignal TransductionTOR Serine-Threonine KinasesAstemizoleCholesterolMTOR protein, humanNiemann-Pick C1 ProteinTOR Serine-Threonine Kinasesangiogenesisastemizolecholesterol traffickingmTORNPC1

Identifiers

PMID30123067
PMCPMC6097475
OpenAlexW2864719721

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.