ArticleHaematologica2019
New thiazolidinones reduce iron overload in mouse models of hereditary hemochromatosis and β-thalassemia.
Article in Haematologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Recent Perspectives on the Physiological and Therapeutic Benefits of Placental Extracts in Chronic Noninfectious Diseases and Aging.Current medicinal chemistry · 2026Pooled it
- Targeting macro- and micro-nutrient regulation of HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Lactate administration improves laboratory parameters in murine models of iron overload.Blood · 2024Article
- Mitochondria as multifaceted regulators of ferroptosis.Life metabolism · 2022Review
- New Deferric Amine Compounds Efficiently Chelate Excess Iron to Treat Iron Overload Disorders and to Prevent Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Novel Insights into Alcoholic Liver Disease: Iron Overload, Iron Sensing and Hemolysis.Journal of translational internal medicine · 2022Article
- A farewell to phlebotomy-use of placenta-derived drugs Laennec and Porcine for improving hereditary hemochromatosis without phlebotomy: a case report.Journal of medical case reports · 2022Article
- Coordination of iron homeostasis by bone morphogenetic proteins: Current understanding and unanswered questions.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Disordered Maternal and Fetal Iron Metabolism Occurs in Preterm Births in Human.Disease markers · 2022Article
- Direct modulation of hepatocyte hepcidin signaling by iron.World journal of hepatology · 2021Article
- The Role of Iron in Benign and Malignant Hematopoiesis.Antioxidants & redox signaling · 2021Review
- SLN124, a GalNac-siRNA targeting transmembrane serine protease 6, in combination with deferiprone therapy reduces ineffective erythropoiesis and hepatic iron-overload in a mouse model of β-thalassaemia.British journal of haematology · 2021Article
- Interplay Between Iron Overload and Osteoarthritis: Clinical Significance and Cellular Mechanisms.Frontiers in cell and developmental biology · 2021Review
- Correcting β-thalassemia by combined therapies that restrict iron and modulate erythropoietin activity.Blood · 2020Article
- Depriving Iron Supply to the Virus Represents a Promising Adjuvant Therapeutic Against Viral Survival.Current clinical microbiology reports · 2020Review
- Iron metabolism and iron disorders revisited in the hepcidin era.Haematologica · 2020Review
- New potential players in hepcidin regulation.Haematologica · 2019Article
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic iron-overload disorders, mainly hereditary hemochromatosis and untransfused β-thalassemia, affect a large population worldwide. The primary etiology of iron overload in these diseases is insufficient production of hepcidin by the liver, leading to excessive intestinal iron absorption and iron efflux from macrophages. Hepcidin agonists would therefore be expected to ameliorate iron overload in hereditary hemochromatosis and β-thalassemia. In the current study, we screened our synthetic library of 210 thiazolidinone compounds and identified three thiazolidinone compounds, 93, 156 and 165, which stimulated hepatic hepcidin production. In a hemochromatosis mouse model with hemochromatosis deficiency, the three compounds prevented the development of iron overload and elicited iron redistribution from the liver to the spleen. Moreover, these compounds also greatly ameliorated iron overload and mitigated ineffective erythropoiesis in β-thalassemic mice. Compounds 93, 156 and 165 acted by promoting SMAD1/5/8 signaling through differentially repressing ERK1/2 phosphorylation and decreasing transmembrane protease serine 6 activity. Additionally, compounds 93, 156 and 165 targeted erythroid regulators to strengthen hepcidin expression. Therefore, our hepcidin agonists induced hepcidin expression synergistically through a direct action on hepatocytes via SMAD1/5/8 signaling and an indirect action via eythroid cells. By increasing hepcidin production, thiazolidinone compounds may provide a useful alternative for the treatment of iron-overload disorders.
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