Evidence map›Paper›PMID 41427359›Full record

ArticlebioRxiv : the preprint server for biology2025

Stereoselective Degradation of Diacylglycerol Kinases Potentiate T cell Activation and Tumor Cell Cytotoxicity.

Minhaj Shaikh, Surya Pravo Mookherjee, Claire C Weckerly, Adam H Libby, Aizhen Xiao, Yunge Zhao, Sagar D Vaidya, AeRyon Kim, Zhihong Li, Madeleine L Ware and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

17 authors.

Minhaj ShaikhDepartment of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
Surya Pravo MookherjeeDepartment of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
Claire C WeckerlyDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.ORCID 0000-0003-2368-8429
Adam H LibbyDepartment of Chemistry, University of Virginia, Charlottesville, VA 22904, USA.
Aizhen XiaoDepartment of Neurology, University of Virginia, Charlottesville, VA 22908, USA.
Yunge ZhaoDepartment of Neurology, University of Virginia, Charlottesville, VA 22908, USA.
Sagar D VaidyaDepartment of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
AeRyon KimDepartment of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
Zhihong LiDepartment of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
Madeleine L WareDepartment of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
Michelle MarantsDepartment of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
Olivia L MurtaghDepartment of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
Wesley J WolfeDepartment of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
Timothy Nj BullockDepartment of Pathology, University of Virginia, Charlottesville, VA 22908, USA.ORCID 0000-0001-6141-3261
Benjamin W PurowDepartment of Neurology, University of Virginia, Charlottesville, VA 22908, USA.
Gerald R V HammondDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.ORCID 0000-0002-6660-3272
Ku-Lung HsuDepartment of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.

Funding

Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI JOHN Hackett BUSHWELLER · 1987 to 2026
$72.1M
Directing Membrane Function with Inositol Lipids in Health and DiseaseR35GM119412 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Gerald R Hammond · 2016 to 2026
$4.3M
Endocannabinoid Biosynthesis in Inflammation and PainR01DA043571 · NIDA · UNIVERSITY OF VIRGINIA · PI Ku-Lung Hsu · 2017 to 2026
$3.5M
Defining and targeting substrate specificity of protein tyrosine phosphatasesR01GM144472 · NIGMS · UNIVERSITY OF VIRGINIA · PI HSU, KU-LUNG · 2022 to 2025
$1.6M
Novel immunotherapeutic potential of DGKalpha inhibition for glioblastomaR01NS126265 · NINDS · UNIVERSITY OF VIRGINIA · PI Benjamin W. Purow · 2023 to 2026
$1.5M
Chemical proteomic investigation of lipid kinase specificity and druggabilityR01AI169412 · NIAID · UNIVERSITY OF VIRGINIA · PI Ku-Lung Hsu · 2023 to 2026
$1.5M
Problem-to-Product Team Entrepreneurship and Active Mentoring (P2P-TEAM) Graduate Training ProgramT32GM139796 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI BRODBELT, JENNIFER S. · 2021 to 2025
$781k
The roles of PLD and DGK isoforms in PIP2 homeostasis during PLC signalingF31HL170755 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WECKERLY, CLAIRE · 2023 to 2025
$126k
NCI NIH HHS P30 CA044579NHLBI NIH HHS F31 HL170755NIAID NIH HHS R01 AI169412NIDA NIH HHS R01 DA043571NIGMS NIH HHS R01 GM144472NIGMS NIH HHS R35 GM119412NIGMS NIH HHS T32 GM139796NINDS NIH HHS R01 NS126265
6 · The paper itself

Abstract

Stereoselective recognition is a powerful means to differentiate selective versus non-specific activity of small molecules in complex biological systems. Here, we disclose stereochemically defined, sulfonyltriazole inhibitors of the lipid enzyme diacylglycerol kinase-alpha (DGKα), a key metabolic checkpoint for T cell effector function. Acute treatment with the covalent DGKα inhibitor AHL-7160 recruited endogenous DGKα to the plasma membrane in a stereoselective and isozyme-specific manner. The membrane translocation activity of AHL-7160 correlated with blockade of cellular phosphatidic acid production and potentiation of primary T cell-mediated killing of a glioblastoma cell line. Quantitative chemoproteomics revealed Y669 and K411 as sites of AHL-7160 modification on endogenous DGKα in cells. Extended treatments resulted in proteasome-dependent and proteome-wide selective degradation of DGKα in T cells. Collectively, these findings establish covalent DGKα ligands as potent molecular glues with translational potential in immunotherapy.

Identifiers

PMID41427359
PMCPMC12713590

What Socratic holds

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LicenceCC BY-NC-ND
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.