ArticleScientific reports2019
Off-target based drug repurposing opportunities for tivantinib in acute myeloid leukemia.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Therapeutic development approaches to treat haploinsufficiency diseases: restoring protein levels.Drug discovery today · 2024Review
- Repurposing of c-MET Inhibitor Tivantinib Inhibits Pediatric Neuroblastoma Cellular Growth.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Article
- Modulators of Wnt Signaling Pathway Implied in Dentin Pulp Complex Engineering: A Literature Review.International journal of molecular sciences · 2022Review
- Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer.Cancers · 2022Article
- MET Inhibition Sensitizes Rhabdomyosarcoma Cells to NOTCH Signaling Suppression.Frontiers in oncology · 2022Article
- Drug Repurposing for Tooth Regeneration: The Promising Premises.Journal of pharmacy & bioallied sciences · 2021Review
- Review
- GSK3α: An Important Paralog in Neurodegenerative Disorders and Cancer.Biomolecules · 2020Review
- Predicting Drug Response and Synergy Using a Deep Learning Model of Human Cancer Cells.Cancer cell · 2020Article
- Establishment and characterization of NCC-ASPS1-C1: a novel patient-derived cell line of alveolar soft-part sarcoma.Human cell · 2020Article
- Drug Repurposing in Dentistry; towards Application of Small Molecules in Dentin Repair.International journal of molecular sciences · 2020Article
- T95 nucleophosmin phosphorylation as a novel mediator and marker of regulated cell death in acute kidney injury.American journal of physiology. Renal physiology · 2020Article
- Synthetic repurposing of drugs against hypertension: a datamining method based on association rules and a novel discrete algorithm.BMC bioinformatics · 2020Article
- Has Drug Repurposing Fulfilled its Promise in Acute Myeloid Leukaemia?Journal of clinical medicine · 2020Review
- Exploring the new horizons of drug repurposing: A vital tool for turning hard work into smart work.European journal of medicinal chemistry · 2019Review
- Tivantinib Hampers the Proliferation of Glioblastoma Cells via PI3K/Akt/Mammalian Target of Rapamycin (mTOR) Signaling.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
GSK3α has been identified as a new target in the treatment of acute myeloid leukemia (AML). However, most GSK3 inhibitors lack specificity for GSK3α over GSK3β and other kinases. We have previously shown in lung cancer cells that GSK3α and to a lesser extent GSK3β are inhibited by the advanced clinical candidate tivantinib (ARQ197), which was designed as a MET inhibitor. Thus, we hypothesized that tivantinib would be an effective therapy for the treatment of AML. Here, we show that tivantinib has potent anticancer activity across several AML cell lines and primary patient cells. Tivantinib strongly induced apoptosis, differentiation and G2/M cell cycle arrest and caused less undesirable stabilization of β-catenin compared to the pan-GSK3 inhibitor LiCl. Subsequent drug combination studies identified the BCL-2 inhibitor ABT-199 to synergize with tivantinib while cytarabine combination with tivantinib was antagonistic. Interestingly, the addition of ABT-199 to tivantinib completely abrogated tivantinib induced β-catenin stabilization. Tivantinib alone, or in combination with ABT-199, downregulated anti-apoptotic MCL-1 and BCL-XL levels, which likely contribute to the observed synergy. Importantly, tivantinib as single agent or in combination with ABT-199 significantly inhibited the colony forming capacity of primary patient AML bone marrow mononuclear cells. In summary, tivantinib is a novel GSK3α/β inhibitor that potently kills AML cells and tivantinib single agent or combination therapy with ABT-199 may represent attractive new therapeutic opportunities for AML.
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Registered trials
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.