Evidence map›Paper›PMID 40706404›Full record

ArticleMolecular pharmacology2025

The thiazolidinedione drug troglitazone inhibits Gq signaling through direct binding to the Gq alpha subunit through inhibition of GDP release.

Naiem T Issa, Tingzhen Shen, Alexander Vizurraga, Alexey Pronin, Taylor Henry, Qiang Wang, Frank E Kwarcinski, Stephan Schürer, Evangelos Badiavas, Gregory G Tall and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 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

11 authors.

Naiem T IssaDepartment of Dermatology, University of Miami Miller School of Medicine, Miami, Florida.
Tingzhen ShenDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan.
Alexander VizurragaDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan.
Alexey ProninDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida.
Taylor HenryDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida.
Qiang WangDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida.
Frank E KwarcinskiDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan.
Stephan SchürerDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida.
Evangelos BadiavasDepartment of Dermatology, University of Miami Miller School of Medicine, Miami, Florida.
Gregory G TallDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan. Electronic address: gregtall@umich.edu.
Vladlen Z SlepakDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida. Electronic address: vslepak@med.miami.edu.

Funding

Investigation of Adhesion GPCR and Ric-8 protein control of heterotrimeric G proteinsR35GM149539 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Gregory Gordon Tall · 2023 to 2026
$2.1M
NIGMS NIH HHS R35 GM149539
6 · The paper itself

Abstract

The cycle of GTP binding and hydrolysis controls heterotrimeric G proteins, and mutations reducing GTPase activity result in constitutive G protein signaling. In Gαq (gene: GNAQ) such mutations cause uveal melanoma and Sturge-Weber syndrome. Finding pharmacological agents that inhibit Gαq will be beneficial for research with therapeutic potential. Previously discovered bacterial depsipeptides (FR900359 and YM-254890) bind directly to Gαq and stabilize its inactive complex with GDP, but suffer from limitations of distribution and bioavailability. We used the established Gαq-YM-254890 complex structure to dock small-molecule drugs into the depsipeptide binding site of Gαq. Our in silico screen of 5000 Food Drug and Administration-approved, experimental, and withdrawn drugs predicted that thiazolidinediones are potential ligands of Gαq. Analysis of G protein coupled receptor-stimulated G protein GTPγS binding demonstrated that troglitazone (441 Da) inhibited Gq nucleotide exchange with the IC

Indexed as

GTP-Binding Protein alpha Subunits, Gq-G11Guanosine DiphosphateSignal TransductionThiazolidinedionesTroglitazoneAnimalsCell Line, TumorDepsipeptidesHEK293 CellsHumansMicePeptides, CyclicProtein BindingDepsipeptidesFR900359GTP-Binding Protein alpha Subunits, Gq-G11Guanosine DiphosphatePeptides, CyclicThiazolidinedionesTroglitazoneYM-254890Drug repurposingG protein inhibitorGuanine nucleotide-binding protein G(q) subunit alphaUveal melanoma

Identifiers

PMID40706404
PMCPMC12489383

What Socratic holds

Textmetadata
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.