Evidence map›Paper›PMID 39723207›Full record

ArticleFrontiers in immunology2024

Linsitinib inhibits proliferation and induces apoptosis of both IGF-1R and TSH-R expressing cells.

Maximilian Luffy, Anna-Lena Ganz, Stefanie Wagner, Jan Wolf, Julian Ropertz, Ryan Zeidan, Jeffrey D Kent, Raymond S Douglas, George J Kahaly

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In one paragraph

Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

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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

9 authors.

Maximilian LuffyMolecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg-University (JGU) Medical Center, Mainz, Germany.
Anna-Lena GanzMolecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg-University (JGU) Medical Center, Mainz, Germany.
Stefanie WagnerMolecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg-University (JGU) Medical Center, Mainz, Germany.
Jan WolfMolecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg-University (JGU) Medical Center, Mainz, Germany.
Julian RopertzMolecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg-University (JGU) Medical Center, Mainz, Germany.
Ryan ZeidanSling Therapeutics, Ann Arbor, MI, United States.
Jeffrey D KentSling Therapeutics, Ann Arbor, MI, United States.
Raymond S DouglasSling Therapeutics, Ann Arbor, MI, United States.
George J KahalyMolecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg-University (JGU) Medical Center, Mainz, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: The insulin-like growth factor 1 receptor (IGF-1R) and the thyrotropin receptor (TSH-R) are expressed on orbital cells and thyrocytes. These receptors are targeted in autoimmune-induced thyroid eye disease (TED). Effective therapeutic treatment of TED inhibits activation of the IGF-1R/TSH-R complex. Methods: The inhibitory effect on cell proliferation of a small molecule targeting IGF-1R phosphorylation (Linsitinib) was investigated in an IGF-1R expressing cell line and a Chinese Hamster Ovary (CHO) cell line overexpressing TSH-R. An IGF-1R monoclonal antibody antagonist, Teprotumumab served as control. Both cell lines were plated in a 96-well format and treated with both compounds for 24 hours. After addition of tetrazolium, absorbance was measured. The apoptosis marker caspase-3/7 activity was measured. The half-maximal inhibitory concentration (IC Results: Linsitinib strongly inhibited the proliferation of both cell lines at several concentrations: 31,612.5 ng/mL (IGF-1R cell line -78%, P=0.0031, TSH-R cell line -75%, P=0.0059), and at 63,225 ng/mL (IGF-1R cell line -73%, P=0.0073, TSH-R cell line -73%, P=0.0108). Linsitinib induced apoptosis of both cell lines, both morphologically confirmed and with an increased caspase-3/7 activity at concentrations of 31,612.5 ng/mL (IGF-1R cell line P=0.0158, TSH-R cell line P=0.0048) and 63,225 ng/mL (IGF-1R cell line P=0.0005, TSH-R cell line P=0.0020). Linsitinib markedly inhibited proliferation of the IGF-1R cell line at all concentrations compared to Teprotumumab (P=0.0286). Teprotumumab inhibition was significant only at 15,806.25 ng/mL with the TSH-R cell line (-15%, P=0.0396). In addition, in the TSH-R-Ab blocking bioassay, Linsitinib and the tested compounds demonstrated strong inhibition across all ten dilutions (100%). Conclusions: Linsitinib effectively induces apoptosis and inhibits proliferation of both IGF-1R and TSH-R expressing target cells, therefore demonstrating its therapeutic potential to block the reported crosstalk of the two mediators in autoimmune TED.

Indexed as

ApoptosisCell ProliferationCricetulusReceptor, IGF Type 1AnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCHO CellsHumansImidazolesPhosphorylationPyrazines3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanolAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedIGF1R protein, humanImidazolesPyrazinesReceptor, IGF Type 1teprotumumabapoptosiscell-based bioassayscell proliferationinsulin-like growth factor 1 receptorLinsitinibsmall molecule kinase inhibitorthyroid eye diseasethyrotropin receptor

Identifiers

PMID39723207
PMCPMC11668815

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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.