Evidence map›Paper›PMID 34298413›Full record

ArticleBioorganic & medicinal chemistry2021

Impact of α-modifications on the activity of triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.

Alisa E R Fairweather, Daniel B Goetz, Chloe M Schroeder, Nazmul H Bhuiyan, Michelle L Varney, David F Wiemer, Sarah A Holstein

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Synthesis of Amino-Pharmaceuticals (Basel, Switzerland) · 2025
    Review
  3. Article
  4. Article
  5. α-Amino bisphosphonate triazoles serve as GGDPS inhibitors.Bioorganic & medicinal chemistry letters · 2024
    Article
  6. Review
  7. Review
  8. Article
  9. 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.

Alisa E R FairweatherDepartment of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
Daniel B GoetzDepartment of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
Chloe M SchroederDepartment of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
Nazmul H BhuiyanDepartment of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
Michelle L VarneyDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
David F WiemerDepartment of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA; Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USA.
Sarah A HolsteinDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: sarah.holstein@unmc.edu.
University of Iowa · USUniversity of Nebraska Medical Center · US

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

Agents that inhibit the enzyme geranylgeranyl diphosphate synthase (GGDPS) have anti-cancer activity and our prior studies have investigated the structure-function relationship for a family of isoprenoid triazole bisphosphonates as GGDPS inhibitors. To further explore this structure-function relationship, a series of novel α-modified triazole phosphonates was prepared and evaluated for activity as GGDPS inhibitors in enzyme and cell-based assays. These studies revealed flexibility at the α position of the bisphosphonate derivatives with respect to being able to accommodate a variety of substituents without significantly affecting potency compared to the parent unsubstituted inhibitor. However, the monophosphonate derivatives lacked activity. These studies further our understanding of the structure-function relationship of the triazole-based GGDPS inhibitors and lay the foundation for future studies evaluating the impact of α-modifications on in vivo activity.

Indexed as

DiphosphonatesDose-Response Relationship, DrugEnzyme InhibitorsFarnesyltranstransferaseHumansMolecular StructureStructure-Activity RelationshipTriazolesDiphosphonatesEnzyme InhibitorsFarnesyltranstransferaseTriazolesBisphosphonateGeranylgeranyl diphosphate synthaseInhibitionIsoprenoid biosynthesisMyelomaTriazole

Identifiers

PMID34298413
PMCPMC8370032
OpenAlexW3177499002

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.