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DHODH Inhibition Suppresses and Inhibits the Growth of Medulloblastoma in a Novel In Vivo Zebrafish Model.
Cancers (Basel)
December 2024
Division of Pediatric Oncology and Pediatric Surgery, Department of Women's and Children's Health, Karolinska Institutet, 171 77 Stockholm, Sweden.
Background/objectives: Medulloblastoma (MB) is the most common high-grade paediatric brain tumour, with group 3 MB patients having the worst prognosis. A high prevalence of group 3 tumours shows overexpression of the oncogene, making it a potential therapeutic target. However, attempts to directly inhibit have so far demonstrated limited success.
View Article and Find Full Text PDFCombination decoction of Astragalus mongholicus and mitigates pressure-overload cardiac dysfunction by inhibiting multiple ferroptosis pathways.
Front Pharmacol
December 2024
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Background: Astragalus mongholicus (AM) and Salvia miltiorrhiza (SM) are commonly used in traditional Chinese medicine to treat heart failure (HF). Ferroptosis has been studied as a key factor in the occurrence of HF. It remains unclear whether the combined use of AM and SM can effectively improve HF and the underlying mechanisms.
View Article and Find Full Text PDFOff-Target Inhibition of Human Dihydroorotate Dehydrogenase (DHODH) Highlights Challenges in the Development of Fat Mass and Obesity-Associated Protein (FTO) Inhibitors.
ACS Pharmacol Transl Sci
December 2024
Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome, 00185 Rome, Italy.
FTO, an -methyladenosine (mA) and ,2'--dimethyladenosine (mA) RNA demethylase, is a promising target for treating acute myeloid leukemia (AML) due to the significant anticancer activity of its inhibitors in preclinical models. Here, we demonstrate that the FTO inhibitor FB23-2 suppresses proliferation across both AML and CML cell lines, irrespective of FTO dependency, indicating an alternative mechanism of action. Metabolomic analysis revealed that FB23-2 induces the accumulation of dihydroorotate (DHO), a key intermediate in pyrimidine nucleotide synthesis catalyzed by human dihydroorotate dehydrogenase (DHODH).
View Article and Find Full Text PDFA CIA strategy with eminent drug-loading capacities for tumor ferroptosis-gas synergistic therapy.
Theranostics
December 2024
Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, 1023 Shatai South Road, Baiyun, Guangzhou, Guangdong 510515, China.
: A common challenge of drug loading and delivery using magnetic resonance imaging (MRI) contrast agents (CAs) is the tendency of aggregation and precipitation at high drug loading conditions. Herein, we propose a generic strategy of controlled ideal aggregation (CIA) to restrict the tendency. : Fe, β-Lapachone (LAP), brequinar (BQR), or Sorafenib (SOR) was respectively loaded onto Gd poly (acrylic acid) macrochelate (GP), an MRI CA, in the hollow core of nitrite-modified hollow mesoporous organosilica nanoparticles (HMON-SNO).
View Article and Find Full Text PDFInhibitors of dihydroorotate dehydrogenase synergize with the broad antiviral activity of 4'-fluorouridine.
Antiviral Res
January 2025
Department of Molecular Oncology, Göttingen Center of Molecular Biosciences (GZMB), University Medical Center Göttingen, Justus-von-Liebig-Weg 11, 37077, Göttingen, Germany; Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, 37077, Göttingen, Germany. Electronic address:
Article Synopsis
- - RNA viruses like influenza and coronaviruses pose significant health threats, often lacking effective vaccines or treatments, while others like filo- and henipaviruses have high mortality rates despite limited outbreaks.
- - The antiviral drug 4'-Fluorouridine (4'-FlU) inhibits RNA virus replication by targeting the RNA-dependent RNA polymerase, but its effectiveness varies across different viruses, necessitating strategies to improve its potency.
- - Researchers found that inhibiting dihydroorotate dehydrogenase (DHODH) enhances the antiviral effects of 4'-FlU against several RNA viruses, including in models of infection, potentially by depleting uridine, which boosts 4'-FlU's incorporation into viral
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