Evidence map›Paper›PMID 31474482›Full record

ArticleBioorganic & medicinal chemistry letters2019

ω-Hydroxy isoprenoid bisphosphonates as linkable GGDPS inhibitors.

Nazmul H Bhuiyan, Michelle L Varney, Deep S Bhattacharya, William M Payne, Aaron M Mohs, Sarah A Holstein, David F Wiemer

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-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

10 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Recent advances in targeted drug delivery systems for multiple myeloma.Journal of controlled release : official journal of the Controlled Release Society · 2024
    Review
  4. α-Amino bisphosphonate triazoles serve as GGDPS inhibitors.Bioorganic & medicinal chemistry letters · 2024
    Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. 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

7 authors at 2 institutions in 1 country.

Nazmul H BhuiyanDepartment of Chemistry, University of Iowa, Iowa City, IA 52242-1294, United States.
Michelle L VarneyDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States.
Deep S BhattacharyaDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States.
William M PayneDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States.
Aaron M MohsDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, United States; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, United States; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, United States.
Sarah A HolsteinDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, United States.
David F WiemerDepartment of Chemistry, University of Iowa, Iowa City, IA 52242-1294, United States; Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, United States. Electronic address: david-wiemer@uiowa.edu.
University of Nebraska Medical Center · USUniversity of Iowa · US

Funding

UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI James Eudy · 1985 to 2026
$55.0M
Project 9 - Renal Drug Targeting for the Treatment of Lupus NephritisP20GM103480 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BRONICH, TATIANA K · 2012 to 2017
$13.3M
Nebraska Center for Nanomedicine- Pilot ProjectsP30GM127200 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI OUPICKY, DAVID · 2018 to 2022
$5.7M
Rab Geranylgeranylation: a Novel Therapeutic Target in Multiple MyelomaR01CA172070 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI HOLSTEIN, SARAH A · 2013 to 2016
$1.3M
NCI NIH HHS P30 CA036727NCI NIH HHS R01 CA172070NIGMS NIH HHS P20 GM103480NIGMS NIH HHS P30 GM127200
6 · The paper itself

Abstract

The enzyme geranylgeranyl diphosphate synthase (GGDPS) is a potential therapeutic target for multiple myeloma. Malignant plasma cells produce and secrete large amounts of monoclonal protein, and inhibition of GGDPS results in disruption of protein geranylgeranylation which in turn impairs intracellular protein trafficking. Our previous work has demonstrated that some isoprenoid triazole bisphosphonates are potent and selective inhibitors of GGDPS. To explore the possibility of selective delivery of such compounds to plasma cells, new analogues with an ω-hydroxy group have been synthesized and examined for their enzymatic and cellular activity. These studies demonstrate that incorporation of the ω-hydroxy group minimally impairs GGDPS inhibitory activity. Furthermore conjugation of one of the novel ω-hydroxy GGDPS inhibitors to hyaluronic acid resulted in enhanced cellular activity. These results will allow future studies to focus on the in vivo biodistribution of HA-conjugated GGDPS inhibitors.

Indexed as

Antineoplastic AgentsApoptosisCell ProliferationDiphosphonatesEnzyme InhibitorsFarnesyltranstransferaseHumansModels, MolecularMolecular StructureMultiple MyelomaProtein PrenylationStructure-Activity RelationshipTerpenesTumor Cells, CulturedAntineoplastic AgentsDiphosphonatesEnzyme InhibitorsFarnesyltranstransferaseTerpenesBisphosphonateGGDP synthaseInhibitionIsoprenoid biosynthesisTriazole

Identifiers

PMID31474482
PMCPMC6936606
OpenAlexW2969625719

What Socratic 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 Socratic graph.