Evidence map›Paper›PMID 21212855›Full record

ArticleACS medicinal chemistry letters2010

The Nitric Oxide Prodrug V-PROLI/NO Inhibits Cellular Uptake of Proline.

Sam Y Hong, Gregory L Borchert, Anna E Maciag, Rahul S Nandurdikar, Joseph E Saavedra, Larry K Keefer, James M Phang, Harinath Chakrapani

Open access · greenAbstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact, top 89% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

8 authors at 3 institutions in 2 countries.

Sam Y HongChemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702.
Gregory L Borchert
Anna E Maciag
Rahul S Nandurdikar
Joseph E Saavedra
Larry K Keefer
James M Phang
Harinath Chakrapani
Science Applications International Corporation (United States) · USFrederick National Laboratory for Cancer Research · USIndian Institute of Science Education and Research Pune · IN

Funding

Using Diazeniumdiolate Chemistry to Design Nitric Oxide-Based TherapiesZIABC005673 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KEEFER, LARRY K · 2009 to 2015
$5.5M
Metabolic Mechanisms for Programmed Cell DeathZIABC010743 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PHANG, JAMES M · 2009 to 2015
$3.1M
Using Diazeniumdiolate Chemistry to Design Nitric Oxide-Based TherapiesZ01BC005673 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KEEFER, LARRY K · 1996 to 2008
$2.9M
Extracellular Matrix and Stress Substrates: the Role of ProlidaseZIABC010746 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PHANG, JAMES M · 2009 to 2015
$1.0M
Intramural NIH HHS Z01 BC005673
6 · The paper itself

Abstract

V-PYRRO/NO is a well studied nitric oxide (NO) prodrug which has been shown to protect human liver cells from arsenic, acetaminophen, and other toxic assaults in vivo. Its proline-based analogue, V-PROLI/NO, was designed to be a more biocompatible form that decomposes to the naturally occurring metabolites of proline, NO, and glycolaldehyde. Like V-PYRRO/NO, this cytochrome P450-activated prodrug was previously assumed to passively diffuse through the cellular membrane. Using (14)C-labeled proline in a competition assay, we show that V-PROLI/NO is transported through proline transporters into multiple cell lines. A fluorescent NO-sensitive dye (DAF-FM diacetate) and nitrite excretion indicated elevated intracellular NO release after metabolism over V-PYRRO/NO. These results also allowed us to predict and design a more permeable analogue, V-SARCO/NO. We report a proline transporter-based strategy for the selective transport of NO prodrugs that may have enhanced efficacy and aid in development of further NO prodrugs with increased permeability.

Identifiers

PMID21212855
PMCPMC3013513
OpenAlexW2016977317

What OpenQuestion holds

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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.