Evidence map›Paper›PMID 29343829›Full record

ArticleScientific reports2018

Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells.

Amila K Nanayakkara, Courtney A Follit, Gang Chen, Noelle S Williams, Pia D Vogel, John G Wise

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed
13.5field-weighted citation impact, top 1% 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

141 citing papers in PubMed, 278 citations in OpenAlex.

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  15. Review
  16. Multidrug Resistance: Are We Still Afraid of the Big Bad Wolf.Pharmaceuticals (Basel, Switzerland) · 2025
    Review
  17. Morellic Acid B OvercomesACS omega · 2025
    Article
  18. Review
  19. Article
  20. Article

81 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Amila K NanayakkaraThe Center for Drug Discovery, Design and Delivery, the Center for Scientific Computing, Southern Methodist University, Dallas, TX, 75275-0376, USA.
Courtney A FollitThe Center for Drug Discovery, Design and Delivery, the Center for Scientific Computing, Southern Methodist University, Dallas, TX, 75275-0376, USA.
Gang ChenThe Center for Drug Discovery, Design and Delivery, the Center for Scientific Computing, Southern Methodist University, Dallas, TX, 75275-0376, USA.
Noelle S WilliamsDepartment of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75390-9038, United States.
Pia D VogelThe Center for Drug Discovery, Design and Delivery, the Center for Scientific Computing, Southern Methodist University, Dallas, TX, 75275-0376, USA. pvogel@smu.edu.
John G WiseThe Center for Drug Discovery, Design and Delivery, the Center for Scientific Computing, Southern Methodist University, Dallas, TX, 75275-0376, USA. jwise@smu.edu.
Southern Methodist University · USSouthwestern Medical Center

Funding

In vitro testing of P-glycoprotein inhibitors identified from in silico databaseR15GM094771 · NIGMS · SOUTHERN METHODIST UNIVERSITY · PI WISE, JOHN GREGORY · 2011 to 2015
$666k
NIGMS NIH HHS R15 GM094771
6 · The paper itself

Abstract

Overexpression of ATP-binding cassette (ABC) transporters is often linked to multidrug resistance (MDR) in cancer chemotherapies. P-glycoprotein (P-gp) is one of the best studied drug transporters associated with MDR. There are currently no approved drugs available for clinical use in cancer chemotherapies to reverse MDR by inhibiting P-glycoprotein. Using computational studies, we previously identified several compounds that inhibit P-gp by targeting its nucleotide binding domain and avoiding its drug binding domains. Several of these compounds showed successful MDR reversal when tested on a drug resistant prostate cancer cell line. Using conventional two-dimensional cell culture of MDR ovarian and prostate cancer cells and three dimensional prostate cancer microtumor spheroids, we demonstrated here that co-administration with chemotherapeutics significantly decreased cell viability and survival as well as cell motility. The P-gp inhibitors were not observed to be toxic on their own. The inhibitors increased cellular retention of chemotherapeutics and reporter compounds known to be transport substrates of P-gp. We also showed that these compounds are not transport substrates of P-gp and that two of the three inhibit P-gp, but not the closely related ABC transporter, ABCG2/BCRP. The results presented suggest that these P-gp inhibitors may be promising leads for future drug development.

Indexed as

Antineoplastic AgentsATP-Binding Cassette, Sub-Family C ProteinsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2Cell Line, TumorCell SurvivalDrug Resistance, MultipleDrug Resistance, NeoplasmHumansInduction ChemotherapyMCF-7 CellsNeoplasm ProteinsAntineoplastic AgentsATP-Binding Cassette, Sub-Family C ProteinsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2Neoplasm Proteins

Identifiers

PMID29343829
PMCPMC5772368
OpenAlexW2783056471

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.