Evidence map›Paper›PMID 37683456›Full record

ArticleBiochemical and biophysical research communications2023

Multimodal action of KRP203 on phosphoinositide kinases in vitro and in cells.

Yoshiki Ikeda, Mindy I Davis, Kazutaka Sumita, Yuxiang Zheng, Satoshi Kofuji, Mika Sasaki, Yoshihisa Hirota, Rajan Pragani, Min Shen, Matthew B Boxer and 4 more

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

Article in Biochemical and biophysical research communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. 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 9 institutions in 2 countries.

Yoshiki IkedaDivision of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA; Institute for Integrated Cell-Material Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
Mindy I DavisNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, 20850, USA.
Kazutaka SumitaDivision of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA; Department of Endovascular Surgery, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Yuxiang ZhengMeyer Cancer Center, Weill Cornell Medicine, New York, NY, 10007, USA.
Satoshi KofujiDivision of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA; Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, 113-8510, Japan.
Mika SasakiDivision of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
Yoshihisa HirotaDivision of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA; Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, Minuma-ku, Saitama, 337-8570, Japan.
Rajan PraganiNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, 20850, USA.
Min ShenNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, 20850, USA.
Matthew B BoxerNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, 20850, USA.
Koh TakeuchiGraduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan.
Toshiya SendaStructural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki, 305-0801, Japan; Department of Accelerator Science, School of High Energy Accelerator Science, The Graduate University for Advanced Studies), Tsukuba, Ibaraki, 305-0801, Japan; Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan.
Anton SimeonovNational Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, 20850, USA.
Atsuo T SasakiDivision of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA; Institute for Advanced Biosciences, Keio University, Tsuruoka, 997-0052, Japan; Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA; Department of Neurosurgery, Brain Tumor Center at UC Gardner Neuroscience Institute, Cincinnati, OH, 45267, USA; Department of Clinical and Molecular Genetics, Hiroshima University Hospital, Hiroshima, 734-8551, Japan. Electronic address: sasakiao@ucmail.uc.edu.
National Institutes of Health · USTokyo Medical and Dental University · JPCornell University · USHigh Energy Accelerator Research Organization · JPKeio University · JPKyoto University · JPShibaura Institute of Technology · JPThe University of Tokyo · JPUniversity of Cincinnati Medical Center · US

Funding

Therapeutic resistance and aggressive malignancy in glioblastomas: the contribution of GTP metabolism through regulation by IMPDH2R01CA255331 · NCI · UNIVERSITY OF CINCINNATI · PI SASAKI, ATSUO · 2021 to 2025
$2.0M
Targeting the Novel PI5P4K Pathway to Induce Glioblastoma SenescenceR01NS089815 · NINDS · UNIVERSITY OF CINCINNATI · PI SASAKI, ATSUO · 2014 to 2018
$1.7M
Mechanistic role of phosphatidylinositol 5-phosphate 4-kinase beta in GTP-dependent lysosomal acidification for stress-resilient cell growth and metabolismR01GM144426 · NIGMS · UNIVERSITY OF CINCINNATI · PI Atsuo Sasaki · 2023 to 2026
$1.7M
NCI NIH HHS R01 CA255331NIGMS NIH HHS R01 GM144426NINDS NIH HHS R01 NS089815
6 · The paper itself

Abstract

Increased phosphoinositide signaling is commonly associated with cancers. While "one-drug one-target" has been a major drug discovery strategy for cancer therapy, a "one-drug multi-targets" approach for phosphoinositide enzymes has the potential to offer a new therapeutic approach. In this study, we sought a new way to target phosphoinositides metabolism. Using a high-throughput phosphatidylinositol 5-phosphate 4-kinase-alpha (PI5P4Kα) assay, we have identified that the immunosuppressor KRP203/Mocravimod induces a significant perturbation in phosphoinositide metabolism in U87MG glioblastoma cells. Despite high sequence similarity of PI5P4K and PI4K isozymes, in vitro kinase assays showed that KRP203 activates some (e.g., PI5P4Kα, PI4KIIβ) while inhibiting other phosphoinositide kinases (e.g., PI5P4Kβ, γ, PI4KIIα, class I PI3K-p110α, δ, γ). Furthermore, KRP203 enhances PI3P5K/PIKFYVE's substrate selectivity for phosphatidylinositol (PI) while preserving its selectivity for PI(3)P. At cellular levels, 3 h of KRP203 treatment induces a prominent increase of PI(3)P and moderate increase of PI(5)P, PI(3,5)P

Indexed as

Phosphatidylinositols1-Phosphatidylinositol 4-KinaseCell Line, TumorFuransGlioblastomaHumansMorpholinesPhosphotransferases (Alcohol Group Acceptor)PyridinesPyrimidines1-Phosphatidylinositol 4-KinaseFuransMorpholinesPhosphatidylinositolsPhosphotransferases (Alcohol Group Acceptor)PI103PyridinesPyrimidinesDrug repurposingDrug screeningKRP203/MocravimodMultitarget drugMulti targetsOne drugPhosphoinositide metabolismPI3KPI3P5K/Type III PIPK/PIKFYVEPI5P4K/Type II PIPK/ phosphatidylinositol 5-phosphate 4-kinasePolypharmacology

Identifiers

PMID37683456
PMCPMC10559341
OpenAlexW4386189741

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.