Evidence map›Paper›PMID 24292071›Full record

ArticleNature chemical biology2014

PITPs as targets for selectively interfering with phosphoinositide signaling in cells.

Aaron H Nile, Ashutosh Tripathi, Peihua Yuan, Carl J Mousley, Sundari Suresh, Iain M Wallace, Sweety D Shah, Denise Teotico Pohlhaus, Brenda Temple, Corey Nislow and 5 more

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.0field-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

32 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Non-Vesicular Lipid Transport Machinery inInternational journal of molecular sciences · 2023
    Review
  7. Article
  8. Article
  9. Regulation of phosphoinositide metabolism in Apicomplexan parasites.Frontiers in cell and developmental biology · 2023
    Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. 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

15 authors at 7 institutions in 2 countries.

Aaron H Nile1] Department of Molecular and Cellular Medicine, Texas A&M University College Station, Texas, USA. [2] Department of Biochemistry and Biophysics, Texas A&M University College Station, Texas, USA. [3] Department of Chemistry, Texas A&M University College Station, Texas, USA. [4] Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Ashutosh Tripathi1] Department of Molecular and Cellular Medicine, Texas A&M University College Station, Texas, USA. [2] Department of Biochemistry and Biophysics, Texas A&M University College Station, Texas, USA. [3] Department of Chemistry, Texas A&M University College Station, Texas, USA. [4] Laboratory for Molecular Modeling, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Peihua Yuan1] Department of Molecular and Cellular Medicine, Texas A&M University College Station, Texas, USA. [2] Department of Biochemistry and Biophysics, Texas A&M University College Station, Texas, USA. [3] Department of Chemistry, Texas A&M University College Station, Texas, USA.
Carl J Mousley1] Department of Molecular and Cellular Medicine, Texas A&M University College Station, Texas, USA. [2] Department of Biochemistry and Biophysics, Texas A&M University College Station, Texas, USA. [3] Department of Chemistry, Texas A&M University College Station, Texas, USA.
Sundari SureshDepartment of Biochemistry, Stanford Genome Technology Center, Stanford University, Palo Alto, California, USA.
Iain M WallaceDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
Sweety D ShahDepartment of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Denise Teotico PohlhausLaboratory for Molecular Modeling, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Brenda TempleR.L. Juliano Structural Bioinformatics Core University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Corey NislowFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Guri GiaeverFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Alexander TropshaLaboratory for Molecular Modeling, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Ronald W DavisDepartment of Biochemistry, Stanford Genome Technology Center, Stanford University, Palo Alto, California, USA.
Robert P St OngeDepartment of Biochemistry, Stanford Genome Technology Center, Stanford University, Palo Alto, California, USA.
Vytas A Bankaitis1] Department of Molecular and Cellular Medicine, Texas A&M University College Station, Texas, USA. [2] Department of Biochemistry and Biophysics, Texas A&M University College Station, Texas, USA. [3] Department of Chemistry, Texas A&M University College Station, Texas, USA. [4] Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
University of North Carolina at Chapel Hill · USPalo Alto University · USTexas A&M University · USUniversity of British Columbia · CAStanford University · USUNC Lineberger Comprehensive Cancer CenterUniversity of Toronto · CA

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Technology to Identify and Assay Chemical Genomic ProbesR01HG003317 · NHGRI · STANFORD UNIVERSITY · PI DAVIS, RONALD WAYNE · 2004 to 2012
$9.1M
Role of the Phospholipids in Golgi Secretory FunctionR01GM044530 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BANKAITIS, VYTAS A · 1991 to 2019
$5.6M
NCI NIH HHS P30 CA016086NHGRI NIH HHS HG003317NHGRI NIH HHS R01 HG003317NIGMS NIH HHS GM44530NIGMS NIH HHS R01 GM044530
6 · The paper itself

Abstract

Sec14-like phosphatidylinositol transfer proteins (PITPs) integrate diverse territories of intracellular lipid metabolism with stimulated phosphatidylinositol-4-phosphate production and are discriminating portals for interrogating phosphoinositide signaling. Yet, neither Sec14-like PITPs nor PITPs in general have been exploited as targets for chemical inhibition for such purposes. Herein, we validate what is to our knowledge the first small-molecule inhibitors (SMIs) of the yeast PITP Sec14. These SMIs are nitrophenyl(4-(2-methoxyphenyl)piperazin-1-yl)methanones (NPPMs) and are effective inhibitors in vitro and in vivo. We further establish that Sec14 is the sole essential NPPM target in yeast and that NPPMs exhibit exquisite targeting specificities for Sec14 (relative to related Sec14-like PITPs), propose a mechanism for how NPPMs exert their inhibitory effects and demonstrate that NPPMs exhibit exquisite pathway selectivity in inhibiting phosphoinositide signaling in cells. These data deliver proof of concept that PITP-directed SMIs offer new and generally applicable avenues for intervening with phosphoinositide signaling pathways with selectivities superior to those afforded by contemporary lipid kinase-directed strategies.

Indexed as

Signal TransductionPhosphatidylinositolsPhospholipid Transfer ProteinsProtein BindingStructure-Activity RelationshipPhosphatidylinositolsPhospholipid Transfer Proteins

Identifiers

PMID24292071
PMCPMC4059020
OpenAlexW1981202925

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.