Evidence map›Paper›PMID 40043324›Full record

ArticleBioorganic & medicinal chemistry2025

Impact of fixed phosphorus position on activity of triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.

Md Ayub Ali, Mona A Maalouf, Dan Feng, Mamunur Rashid, Nathaniel R Gehrke, Yashpal S Chhonker, Daryl J Murry, David F Wiemer, Sarah A Holstein

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

9 authors.

Md Ayub AliDepartment of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA; Department of Chemistry, Bangladesh University of Engineering and Technology (BUET), Dhaka 1000, Bangladesh.
Mona A MaaloufDepartment of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
Dan FengDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Mamunur RashidDepartment of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE, USA.
Nathaniel R GehrkeDepartment of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
Yashpal S ChhonkerDepartment of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE, USA.
Daryl J MurryDepartment of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
David F WiemerDepartment of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
Sarah A HolsteinDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: sarah.holstein@unmc.edu.

Funding

UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI James Eudy · 1985 to 2026
$55.0M
Geranylgeranyl diphosphate synthase inhibitor therapy for multiple myelomaR01CA258621 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI HOLSTEIN, SARAH A, MOHS, AARON M. · 2021 to 2025
$2.5M
NCI NIH HHS P30 CA036727NCI NIH HHS R01 CA258621
6 · The paper itself

Abstract

Geranylgeranyl diphosphate synthase (GGDPS) produces the 20-carbon isoprenoid species used in protein geranylgeranylation reactions. Inhibition of GGDPS has emerged as a novel means of disrupting the activity of geranylgeranylated proteins in cancers such as myeloma and osteosarcoma. We have focused on developing a series of isoprenoid triazole bisphosphonate-based GGDPS inhibitors, demonstrating a complex structure-activity relationship (SAR), not only at the enzymatic level, but also at the cellular and whole organism levels. To further investigate this SAR, we have prepared a family of novel derivatives that have a fixed phosphorus position by virtue of vinyl, epoxy or cyclopropyl groups that incorporate the α-carbon position. Additional modifications include compounds with homocitronellyl chains instead of homogeranyl or homoneryl chains. All new compounds were evaluated in GGDPS enzyme assays and in cellular assays involving a panel of human myeloma and osteosarcoma cell lines. The homocitronellyl derivatives displayed markedly reduced activity in both enzymatic and cellular assays. While all of the homogeranyl/homoneryl vinyl/epoxy/cyclopropyl compounds had relatively similar activity in the enzyme assay (IC

Indexed as

DiphosphonatesEnzyme InhibitorsFarnesyltranstransferaseTriazolesCell Line, TumorDose-Response Relationship, DrugHumansMolecular StructureStructure-Activity RelationshipDiphosphonatesEnzyme InhibitorsFarnesyltranstransferaseTriazolesGGDP synthaseInhibitionIsoprenoid biosynthesisPermeabilityTriazole

Identifiers

PMID40043324
PMCPMC12090098

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.