Evidence map›Paper›PMID 42084925›Full record

ArticleJCI insight2026

Development and characterization of triazole-based WDR5 inhibitors for the treatment of glioblastoma.

Jesse A Coker, Steven R Martinez, Sang Hoon Han, Anthony R Sloan, Amit Kumar Gupta, George Bukenya, Paul Polzer, James H Ramos, Emma G Rico, Annabella Rico and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

24 authors.

Jesse A CokerDepartment of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
Steven R MartinezCleveland Clinic Center for Therapeutics Discovery (C3TD), Cleveland Clinic Research, Cleveland, Ohio, USA.
Sang Hoon HanCleveland Clinic Center for Therapeutics Discovery (C3TD), Cleveland Clinic Research, Cleveland, Ohio, USA.
Anthony R SloanDepartment of Cardiovascular Medicine, Cleveland Clinic Research, Cleveland, Ohio, USA.
Amit Kumar GuptaCleveland Clinic Genome Center and.
George BukenyaDepartment of Cardiovascular Medicine, Cleveland Clinic Research, Cleveland, Ohio, USA.
Paul PolzerCleveland Clinic Center for Therapeutics Discovery (C3TD), Cleveland Clinic Research, Cleveland, Ohio, USA.
James H RamosDepartment of Cardiovascular Medicine, Cleveland Clinic Research, Cleveland, Ohio, USA.
Emma G RicoCleveland Clinic Center for Therapeutics Discovery (C3TD), Cleveland Clinic Research, Cleveland, Ohio, USA.
Annabella RicoCleveland Clinic Center for Therapeutics Discovery (C3TD), Cleveland Clinic Research, Cleveland, Ohio, USA.
A Abigail LindseyCleveland Clinic Center for Therapeutics Discovery (C3TD), Cleveland Clinic Research, Cleveland, Ohio, USA.
Tanvi NavadgiDepartment of Cardiovascular Medicine, Cleveland Clinic Research, Cleveland, Ohio, USA.
Natalie ReitzDepartment of Cardiovascular Medicine, Cleveland Clinic Research, Cleveland, Ohio, USA.
Todd RomighCleveland Clinic Center for Therapeutics Discovery (C3TD), Cleveland Clinic Research, Cleveland, Ohio, USA.
Jonathan MacdonaldCleveland Clinic Center for Therapeutics Discovery (C3TD), Cleveland Clinic Research, Cleveland, Ohio, USA.
Dhiraj SonawaneCleveland Clinic Center for Therapeutics Discovery (C3TD), Cleveland Clinic Research, Cleveland, Ohio, USA.
Christopher M GoinsDepartment of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
Christopher G HubertCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA.
Nancy S WangCleveland Clinic Center for Therapeutics Discovery (C3TD), Cleveland Clinic Research, Cleveland, Ohio, USA.
Feixiong ChengDepartment of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
Joseph AlvaradoDepartment of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
Samuel A SprowlsPASS Division and.
Justin D LathiaDepartment of Cardiovascular Medicine, Cleveland Clinic Research, Cleveland, Ohio, USA.
Shaun R StaufferDepartment of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma (GBM) cancer stem cells (CSCs) contribute to tumor recurrence, treatment resistance, and dismal clinical outcomes. Genetic and pharmacological evidence suggests that the nuclear scaffolding protein WD-repeat containing protein 5 (WDR5) is a therapeutic vulnerability of the CSC population. However, previously reported WDR5 inhibitors display low permeability and are unable to penetrate the blood-brain barrier (BBB), limiting their utility in GBM. Herein, we report the structure-guided development of a series of triazole-based WDR5 WIN-site inhibitors designed to increase passive brain penetration. We identified triazole-based WDR5 inhibitors that are potent, passively permeable, and in some cases more brain penetrant than other scaffolds. We phenotypically assessed our WDR5 inhibitors in a panel of patient-derived CSC models and uncovered unique WDR5-regulated metabolic genes in GBM. We also evaluated their antiproliferative activity against CSCs both in vitro and in vivo. Finally, to identify potential combination opportunities, we screened a 2,100-compound chemical probe library and identified that the ATAD2 inhibitor BAY-850 synergizes with WDR5 inhibitors to enhance CSC killing. Our work diversifies the chemical matter targeting WDR5, clarifies the in vitro consequences of WIN-site inhibition in CSCs, and encourages the future development of next-generation WDR5 inhibitors with the potential to achieve in vivo efficacy in the brain.

Indexed as

Antineoplastic AgentsBrain NeoplasmsGlioblastomaIntracellular Signaling Peptides and ProteinsTriazolesAnimalsBlood-Brain BarrierCell Line, TumorCell ProliferationHumansMiceNeoplastic Stem CellsXenograft Model Antitumor AssaysAntineoplastic AgentsIntracellular Signaling Peptides and ProteinsTriazolesWDR5 protein, humanBrain cancerCell biologyNeuroscienceOncologyStructural biologyTherapeutics

Identifiers

PMID42084925
PMCPMC13313556

What Socratic holds

Textmetadata
LicenceCC BY
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.