Evidence map›Paper›PMID 28853901›Full record

ArticleMolecular pharmaceutics2018

Pharmacological, Physiochemical, and Drug-Relevant Biological Properties of Short Chain Fatty Acid Hexosamine Analogues Used in Metabolic Glycoengineering.

Christopher T Saeui, Lingshu Liu, Esteban Urias, Justin Morrissette-McAlmon, Rahul Bhattacharya, Kevin J Yarema

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

Article in Molecular pharmaceutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Improving Immunotherapy Through Glycodesign.Frontiers in immunology · 2018
    Review
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 1 institution in 1 country.

Christopher T SaeuiDepartment of Biomedical Engineering and the Translational Tissue Engineering Center , The Johns Hopkins University , Baltimore , Maryland 21231 , United States.ORCID 0000-0002-4753-3862
Lingshu LiuDepartment of Biomedical Engineering and the Translational Tissue Engineering Center , The Johns Hopkins University , Baltimore , Maryland 21231 , United States.
Esteban UriasDepartment of Biomedical Engineering and the Translational Tissue Engineering Center , The Johns Hopkins University , Baltimore , Maryland 21231 , United States.
Justin Morrissette-McAlmonDepartment of Biomedical Engineering and the Translational Tissue Engineering Center , The Johns Hopkins University , Baltimore , Maryland 21231 , United States.
Rahul BhattacharyaDepartment of Biomedical Engineering and the Translational Tissue Engineering Center , The Johns Hopkins University , Baltimore , Maryland 21231 , United States.ORCID 0000-0002-1267-3638
Kevin J YaremaDepartment of Biomedical Engineering and the Translational Tissue Engineering Center , The Johns Hopkins University , Baltimore , Maryland 21231 , United States.
Johns Hopkins University · US

Funding

Probing the Connections between Monosaccharide Analogs, Sialic Acid Metabolism, aR01CA112314 · NCI · JOHNS HOPKINS UNIVERSITY · PI YAREMA, KEVIN J · 2005 to 2022
$4.5M
AGX1/2 inhibitors as key modulators of the hexosamine biosynthetic pathwayR21CA191715 · NCI · JOHNS HOPKINS UNIVERSITY · PI YAREMA, KEVIN J · 2015 to 2016
$388k
Inhibiting UAP1/2 as a Novel Strategy for Regulating Carbohydrate Metabolic FluxF31CA192767 · NCI · JOHNS HOPKINS UNIVERSITY · PI SAEUI, CHRISTOPHER · 2015 to 2016
$87k
NCI NIH HHS F31 CA192767NCI NIH HHS R01 CA112314NCI NIH HHS R21 CA191715
6 · The paper itself

Abstract

In this study, we catalog structure activity relationships (SAR) of several short chain fatty acid (SCFA)-modified hexosamine analogues used in metabolic glycoengineering (MGE) by comparing in silico and experimental measurements of physiochemical properties important in drug design. We then describe the impact of these compounds on selected biological parameters that influence the pharmacological properties and safety of drug candidates by monitoring P-glycoprotein (Pgp) efflux, inhibition of cytochrome P450 3A4 (CYP3A4), hERG channel inhibition, and cardiomyocyte cytotoxicity. These parameters are influenced by length of the SCFAs (e.g., acetate vs n-butyrate), which are added to MGE analogues to increase the efficiency of cellular uptake, the regioisomeric arrangement of the SCFAs on the core sugar, the structure of the core sugar itself, and by the type of N-acyl modification (e.g., N-acetyl vs N-azido). By cataloging the influence of these SAR on pharmacological properties of MGE analogues, this study outlines design considerations for tuning the pharmacological, physiochemical, and the toxicological parameters of this emerging class of small molecule drug candidates.

Indexed as

Drug DesignAnimalsAnimals, NewbornATP Binding Cassette Transporter, Subfamily BCells, CulturedCytochrome P-450 CYP3ACytochrome P-450 CYP3A InhibitorsDrug Evaluation, PreclinicalFatty Acids, VolatileHexosaminesMetabolic EngineeringMolecular StructureMyocytes, CardiacPrimary Cell CultureRatsStructure-Activity RelationshipABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BCytochrome P-450 CYP3ACytochrome P-450 CYP3A InhibitorsERG protein, humanFatty Acids, VolatileHexosaminesTranscriptional Regulator ERGcarbohydrate drug designhERGmetabolic oligosaccharide engineeringP450Pgp efflux

Identifiers

PMID28853901
PMCPMC6292510
OpenAlexW2751502661

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.