Evidence map›Paper›PMID 41925966›Full record

ArticleEndocrine2026

The pyrazolo[3,4-d]pyrimidine derivative CLM24 has an antineoplastic effect in aggressive dedifferentiated thyroid cancer in vitro.

Silvia Martina Ferrari, Francesca Ragusa, Giusy Elia, Valeria Mazzi, Eugenia Balestri, Chiara Botrini, Licia Rugani, Simona Piaggi, Concettina La Motta, Giulia Antonelli and 11 more

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

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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

21 authors.

Silvia Martina FerrariDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Francesca RagusaDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Giusy EliaDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Valeria MazziDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Eugenia BalestriDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Chiara BotriniDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Licia RuganiDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Simona PiaggiDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, 56126, Italy.
Concettina La MottaDepartment of Pharmacy, University of Pisa, Pisa, 56126, Italy.
Giulia AntonelliDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Salvatore UlisseDepartment of Surgery, "Sapienza" University of Rome, Rome, 00161, Italy.
Camilla ViriliDepartment of Medico-Surgical Sciences and Biotechnologies, Endocrinology Section, "Sapienza" University of Rome, Latina, 04100, Italy.
Gilda VarricchiDepartment of Translational Medical Sciences, Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Giulia CantiniDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, 50139, Italy.
Oriana FabrazzoDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Elena Catania RomiziDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Maria Giorgia MartinoDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Michaela LuconiDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, 50139, Italy.
Gabriele MaterazziDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy.
Alessandro AntonelliDepartment of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 56126, Italy. alessandro.antonelli@unipi.it.
Poupak FallahiDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, 56126, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeCompounds with a pyrazolo[3,4-d]pyrimidine nucleus (CLM24, CLM3, and CLM29) with inhibitory activities towards RET protein kinases, EGFR, VEGFR and as antiangiogenic agents had been evaluated in preceding researches in experimental models of thyroid cancer (TC) in vitro and in vivo. Here, we designed a study to evaluate the antineoplastic activity of CLM24 in vitro in primary dedifferentiated thyroid carcinoma (DeDTC) cells and in the AF cell line (a continuous ATC cell line previously obtained from a patient-derived cell culture and immortalized in vitro).

methodsWe investigated in vitro CLM24 in human primary cultures from 10 patients with DeDTC and 5 healthy controls, and in the continuous AF cell line (as a comparative reference), evaluating its effect on cell proliferation, apoptosis, migration/invasion, and VEGF-A expression.

resultsCLM24 showed a significant antiproliferative effect on the AF cell line (harboring the BRAF p.V600E mutation), along with a marked pro-apoptotic activity. In primary DeDTC cells with/without BRAF p.V600E mutation, CLM24 significantly reduced cell proliferation compared with controls, whereas no effect was observed in primary normal thyrocytes. In DeDTC cells with/without BRAF p.V600E mutation, the proportion of apoptotic cells increased in a dose-dependent manner following CLM24 treatment, which also significantly inhibited cell migration/invasion. Furthermore, CLM24 reduced significantly VEGF-A expression in DeDTC cells, especially at higher concentrations.

conclusionCLM24 exhibited a potent antineoplastic effect in vitro in primary DeDTC cells, regardless of the presence of the BRAF p.V600E mutation. These encouraging results suggest further studies to assess CLM24 in a possible clinical trial setting.

Indexed as

Antineoplastic AgentsPyrazolesPyrimidinesThyroid NeoplasmsAgedApoptosisCell Line, TumorCell MovementCell ProliferationFemaleHumansMaleMiddle AgedProto-Oncogene Proteins B-rafVascular Endothelial Growth Factor AAntineoplastic AgentsProto-Oncogene Proteins B-rafPyrazolespyrazolo(3,4-d)pyrimidinePyrimidinesVascular Endothelial Growth Factor ACLM24dedifferentiated aggressive thyroid cancerprimary cell culturespyrazolo(3,4-d)pyrimidine derivativestyrosine kinase inhibitors

Identifiers

PMID41925966

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