Evidence map›Paper›PMID 30639261›Full record

ArticleCell chemical biology2019

Discovery of Small-Molecule Inhibitors of the HSP90-Calcineurin-NFAT Pathway against Glioblastoma.

Zhenzhen Liu, Hongli Li, Lian He, Yu Xiang, Chengsen Tian, Can Li, Peng Tan, Ji Jing, Yanpin Tian, Lupei Du and 4 more

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

Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

19 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
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  11. Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Article
  12. Review
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  18. Molecular chaperones in the brain endothelial barrier: neurotoxicity or neuroprotection?FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Review
  19. Article
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

14 authors at 7 institutions in 2 countries.

Zhenzhen LiuInstitute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA; Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China; Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan, Shandong 250014, China.
Hongli LiInstitute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA; Department of Histology and Embryology, Army Medical University, Chongqing 400038, China.
Lian HeInstitute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA.
Yu XiangDepartment of Biochemistry and Molecular Biology, McGovern Medical School at the University of Texas Health Science Center, Houston, TX 77030, USA.
Chengsen TianDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China; School of Chemistry and Chemical Engineering, Qilu Normal University, Jinan, Shandong 250200, China.
Can LiInstitute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA.
Peng TanInstitute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA.
Ji JingInstitute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA.
Yanpin TianDepartment of Histology and Embryology, Army Medical University, Chongqing 400038, China.
Lupei DuDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China.
Yun HuangInstitute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA.
Leng HanDepartment of Biochemistry and Molecular Biology, McGovern Medical School at the University of Texas Health Science Center, Houston, TX 77030, USA. Electronic address: leng.han@uth.tmc.edu.
Minyong LiDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong 250100, China. Electronic address: mli@sdu.edu.cn.
Yubin ZhouInstitute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA; Department of Medical Physiology, College of Medicine, Texas A&M University, Temple, TX 76504, USA. Electronic address: yzhou@ibt.tamhsc.edu.
Texas A&M University · USShandong University · CNArmy Medical University · CNTexas A&M University System · USTexas Medical Center · USThe University of Texas Health Science Center · USThe University of Texas Health Science Center at Houston · US

Funding

MOLECULAR CONTROL OF CALCIUM INFLUX AT THE ER-PLASMA MEMBRANE JUNCTIONSR01GM112003 · NIGMS · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI ZHOU, YUBIN · 2014 to 2022
$2.7M
TET-mediated epigenetic regulation in cardiac development.R01HL134780 · NHLBI · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI HUANG, YUN · 2018 to 2022
$1.9M
Optogenetic toolkit for remote control of voltage-gated calcium channelsR21GM126532 · NIGMS · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI HAN, GANG, ZHOU, YUBIN · 2018 to 2019
$443k
NHLBI NIH HHS R01 HL134780NIGMS NIH HHS R01 GM112003NIGMS NIH HHS R21 GM126532
6 · The paper itself

Abstract

Glioblastoma (GBM) is among the most common and malignant types of primary brain tumors in adults, with a dismal prognosis. Although alkylating agents such as temozolomide are widely applied as the first-line treatment for GBM, they often cause chemoresistance and remain ineffective with recurrent GBM. Alternative therapeutics against GBM are urgently needed in the clinic. We report herein the discovery of a class of inhibitors (YZ129 and its derivatives) of the calcineurin-NFAT pathway that exhibited potent anti-tumor activity against GBM. YZ129-induced GBM cell-cycle arrest at the G2/M phase promoted apoptosis and inhibited tumor cell proliferation and migration. At the molecular level, YZ129 directly engaged HSP90 to antagonize its chaperoning effect on calcineurin to abrogate NFAT nuclear translocation, and also suppressed other proto-oncogenic pathways including hypoxia, glycolysis, and the PI3K/AKT/mTOR signaling axis. Our data highlight the potential for targeting the cancer-promoting HSP90 chaperone network to treat GBM.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCalcineurinCalciumCell Line, TumorCell MovementDrug Evaluation, PreclinicalDrug Resistance, NeoplasmG2 Phase Cell Cycle CheckpointsGlioblastomaGlycolysisHSP90 Heat-Shock ProteinsHumansMiceMice, NudeAntineoplastic AgentsCalcineurinCalciumHSP90 Heat-Shock ProteinsNFATC Transcription FactorsSmall Molecule Librariescalcineurincancer therapycell signalingclick chemistrydrug screeninggene expressionglioblastomaHSP90 inhibitorNFATproteomics

Identifiers

PMID30639261
PMCPMC6430684
OpenAlexW2910341542

What OpenQuestion holds

Textmetadata
LicenceTDM
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.