Ask about this productRelated genes to: DHODH Blocking Peptide
- Gene:
- DHODH NIH gene
- Name:
- dihydroorotate dehydrogenase (quinone)
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 16q22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-06-29
- Date modifiied:
- 2015-09-11
Related products to: DHODH Blocking Peptide
Related articles to: DHODH Blocking Peptide
- Alveolar echinococcosis (AE) is a serious zoonotic parasitic disease caused by the larvae of Echinococcus multilocularis. Given the limitations of current medications, there is an urgent necessity for the development of novel pharmacological treatments for AE. Azithromycin, a macrolide antibiotic, exhibits both antibacterial and antiparasitic effects. This study aimed to investigate its effects on the viability of E. multilocularis protoscoleces (EmPSCs) and to elucidate the underlying mechanisms. Ultrastructural changes were examined using scanning and transmission electron microscopy. Glucose assays, reactive oxygen species (ROS) assays, mitochondrial membrane potential (MMP) assays, and Western blot were used to evaluate the in vitro effects of azithromycin on EmPSCs. Our results demonstrated that azithromycin treatment significantly decreased the viability of EmPSCs and caused pronounced ultrastructural damage. Mechanistically, it significantly downregulated glucose transporter 1 (GLUT1) and protein kinase B (AKT) signaling, elevated ROS levels (P < 0.001), and decreased MMP. Furthermore, Azithromycin treatment significantly elevated the expression of the DNA damage marker γ-H2AX (P < 0.001), while also increasing lipid peroxidation and Fe²⁺ levels, depleting GSH content, and downregulating GPX4 and DHODH expression(P < 0.001). Collectively, azithromycin may exert multiple effects on EmPSCs in vitro, encompassing glucose metabolic disruption, oxidative stress, and ferroptosis. - Source: PubMed
Publication date: 2026/09/23
Liao XiaZhao JinlongFang ZiyiDu YunAbulaiti MaierhabaQiu TengfeiJia YutongSimayili NazhaketiZhao JunLin RenyongLü Guodong - BRAF V600E occurs in selected primary central nervous system (CNS) tumors and in a subset of thyroid cancers that can metastasize to the brain, but the shared alteration does not make these diseases biologically equivalent. This Mini Review examines programmed cell death evasion in pleomorphic xanthoastrocytoma and ganglioglioma, with selected molecular and clinical comparisons involving epithelioid glioblastoma, pilocytic astrocytoma, pediatric low-grade glioma, and thyroid cancer brain metastases (TCBM). Evidence linking BRAF-MEK-ERK signaling to apoptosis is strongest in non-CNS thyroid cancer and other BRAF-mutant models; direct validation in TCBM remains limited. Ferroptosis sensitization has been demonstrated preclinically in BRAF V600E anaplastic thyroid cancer outside the brain, whereas the ferroptosis suppressor protein 1 (FSP1)/coenzyme Q10 (CoQ10) axis and dihydroorotate dehydrogenase (DHODH) remain general mechanistic frameworks rather than established dependencies in the target CNS settings. Clinical studies support BRAF/MEK inhibition in BRAF V600E-mutant glioma and systemic anaplastic thyroid cancer, but direct TCBM intracranial evidence is restricted to very limited, confounded observations. The intact blood-brain barrier, heterogeneous blood-tumor barrier, efflux transporters, and brain microenvironment further complicate inference from systemic outcomes. We therefore separate direct, indirect, and hypothesis-generating evidence and identify disease-specific pharmacokinetic, mechanistic, and prospective clinical studies as priorities. - Source: PubMed
Publication date: 2026/09/02
Jin TongLv YuanshiYang QiushiZhang RuiJin Hui - Arginine metabolism, polyamine homeostasis and ferroptosis are interconnected molecular processes that influence tumor growth, immune remodeling and therapeutic responses. The availability of arginine is affected by tumor‑cell biosynthesis and uptake, myeloid arginase (ARG)‑mediated depletion, nitric oxide synthase (NOS)‑driven diversion and stromal‑vascular nutrient transport and microenvironmental remodeling. These input signals regulate the synthesis, uptake‑efflux cycling and catabolic turnover of polyamines, thereby creating an inhibitory buffering state or an oxidative state that can lower the ferroptosis threshold. Ferroptosis is controlled by the balance of lipid peroxidation triggers, including polyunsaturated fatty acid‑phospholipid load, iron‑dependent amplification and lipoxygenase activity, as well as buffering systems such as the cystine/glutamate antiporter system Xc-‑glutathione‑glutathione peroxidase 4 axis, ferroptosis suppressor protein 1‑coenzyme Q10, dihydroorotate dehydrogenase and GTP cyclohydrolase 1‑tetrahydrobiopterin (BH4). The immunological consequences of ferroptotic tumor‑cell death are context‑dependent, as dying cells may promote interferon‑gamma‑driven antitumor immunity or, conversely, reinforce myeloid‑mediated immunosuppression. The present review summarized the molecular links among arginine metabolism, polyamine homeostasis and ferroptosis in cancer and discusses therapeutic opportunities involving biomarker‑guided combinations targeting arginine, polyamine blockade, ferroptosis sensitization and immune checkpoint blockade. - Source: PubMed
Publication date: 2026/09/18
Dong XinHou YongkunShao JingjingZhu HaixiaLiu Jibin - Macropinocytosis enables cancer cells to scavenge extracellular nutrients and contributes to tumor progression, but its role in chemoresistance remains poorly characterized. Through CRISPR-Cas9 and small-molecule screens, we identify inhibition of dihydroorotate dehydrogenase (DHODH), an enzyme in pyrimidine synthesis, as an inducer of macropinocytosis. Mechanistically, DHODH inhibition triggers metabolic reprogramming toward glycolysis and lactate accumulation. This metabolic shift promotes lysine 208 lactylation of telomeric repeat-binding factor 2-interacting protein (TERF2IP), unveiling its moonlighting function in transcriptional activation of epiregulin, which activates EGFR signaling to promote macropinocytosis. Macropinosomes contact mitochondria, enabling albumin translocation into the mitochondrial intermembrane space where it interacts with DHODH, diminishing inhibitor binding and restoring DHODH activity. This adaptive response contributes to drug resistance in vitro and in vivo, and co-administration of DHODH inhibitors with macropinocytosis blockers or EGFR inhibitors enhances anti-tumor efficacy. Our findings reveal a previously unknown metabolic stress-induced macropinocytosis pathway and provide a rationale for combination therapy to enhance DHODH inhibitor efficacy in cancer treatment. - Source: PubMed
Publication date: 2026/08/14
Yuan JunhuWang TanMa YaruiLi GuangyuWang ChenxiLiu MeiCai ZianWang XiaoyueWang XiaobingWang HongyingJiao Yuchen - Pyrimidine metabolism is crucial for the replication of viruses and the functionality of host cells. However, the cell-type-specific organization of this metabolism in the central nervous system and its dysregulation during Japanese encephalitis virus (JEV) infection remain poorly understood. Here, we aimed to characterize the cell-type-specific landscape of pyrimidine metabolism in the CNS and uncover pyrimidine metabolic reprogramming during JEV infection. - Source: PubMed
Publication date: 2026/07/31
Gu JunFan ChenchengXiang ShengxianSi YouhuiZhu BiboCao ShengboYe Jing