Evidence map›Paper›PMID 41351922›Full record

ArticleEuropean journal of medicinal chemistry2026

Design, synthesis, and biological properties exhibited by 1,2,3-triazole based Grp94-selective inhibitors.

Hao Xu, Dustin J E Huard, Elijah Dunn, Lucas A Chalfoun, Felix Adulley, Raquel L Lieberman, Brian S J Blagg

Abstract read
In one paragraph

Article in European journal of medicinal chemistry, 2026. 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. 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

7 authors.

Hao XuDepartment of Chemistry and Biochemistry, Warren Center for Drug Discovery, The University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.
Dustin J E HuardSchool of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Elijah DunnSchool of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Lucas A ChalfounDepartment of Chemistry and Biochemistry, Warren Center for Drug Discovery, The University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.
Felix AdulleyDepartment of Chemistry and Biochemistry, Warren Center for Drug Discovery, The University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.
Raquel L LiebermanSchool of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Brian S J BlaggDepartment of Chemistry and Biochemistry, Warren Center for Drug Discovery, The University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA. Electronic address: bblagg@nd.edu.

Funding

Selective Inhibition of GRP 94 to Treat Ocular Hypertension and GlaucomaR01EY036107 · NEI · UNIVERSITY OF NOTRE DAME · PI Brian S J Blagg, Raquel L Lieberman · 2024 to 2026
$1.8M
NEI NIH HHS R01 EY036107
6 · The paper itself

Abstract

Grp94, the endoplasmic reticulum-resident paralog of Hsp90, is responsible for the folding and maturation of several client proteins including integrins and mutant myocilin. Inhibition of Grp94 with small molecules has been shown to reduce cell migration of breast cancer cells and promote degradation of mutant myocilin aggregates. Herein, we describe the development of 1,2,3-triazole based Grp94-selective inhibitors derived from a nitrogen scan on BnIm. Structure-activity relationship studies identified lead compound 47, which manifests 76 nM affinity for Grp94 with 121-fold selectivity over Hsp90α. In cellular studies, compound 47 induced the degradation of integrin α2 in MDA-MB-231 cells and reduced intracellular accumulation of mutant myocilin in human trabecular meshwork cells. These findings supported compound 47 as a potent and selective Grp94-selective inhibitor with therapeutic potential.

Indexed as

Drug DesignMembrane GlycoproteinsTriazolesAntineoplastic AgentsCell Line, TumorDose-Response Relationship, DrugHumansMolecular StructureStructure-Activity RelationshipAntineoplastic AgentsendoplasminMembrane GlycoproteinsTriazolesGlucose regulated-protein 94 (Grp94)Heat shock protein 90 (Hsp90)IntegrinMetastatic cancerMutant myocilinOpen-angle glaucoma

Identifiers

PMID41351922
PMCPMC13205134

What OpenQuestion holds

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LicenceCC BY
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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.