Ask about this productRelated genes to: DHODH antibody
- 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 antibody
Related articles to: DHODH antibody
- The autoimmune hair loss disorder alopecia areata (AA), is characterized by immune privilege (IP) collapse of the hair follicle (HF) bulb resulting from a Th1-dependent inflammatory response. Although CD8 T cells are recognized key drivers of the disease, it remains to be clarified whether the activation of HF resident T cells suffice to initiate IP loss and thus elicit the cascade of events leading to AA. Here, we utilized the human microdissected HF organ culture model to answer this question by activating intra- and peri-follicular HF resident T cells with αCD3/αCD28 antibodies. TCR stimulation indeed resulted in enhanced resident T cell proliferation, as indicated by significantly increased CD3Ki-67 cells, and higher intrafollicular CD3 T cell numbers. Furthermore, αCD3/αCD28 stimulation promoted key signs of HF IP collapse, by increasing bulbar MHC class I and II expression and elevating MHC class II cells numbers. We next sought to investigate whether T cell proliferation plays a central role in the TCR activation-dependent collapse of the bulb IP. To test this, we co-administered the DHODH inhibitor farudodstat 1 day prior and during the stimulation with αCD3/αCD28 in HF organ culture. Short-term treatment with farudodstat reduced the increase in T cell proliferation and significantly decreased the upregulated MHC class I and II expression induced by TCR stimulation with αCD3/αCD28. Our results show that stimulation of HF resident T cells via TCR engagement induces an AA-like phenotype in healthy human HFs , characterized by T cell proliferation and subsequent IP collapse. DHODH inhibition with farudodstat only partially reduces T cell numbers but prevented HF IP collapse induction. - Source: PubMed
Publication date: 2026/04/29
Piccini IlariaRouillé ThomasFunk WolfgangJimenez FranciscoKaoukhov AlexandreFirth CarlGilhar AmosEdelkamp JaninCevikbas FerdaBertolini Marta - Targeting cancer metabolism, particularly de novo nucleotide biosynthesis, has emerged as a promising and innovative therapeutic strategy for both hematologic and solid malignancies, including those of the Central Nervous System (CNS). Glioblastoma cancer stem-like cells are especially vulnerable to pyrimidine synthesis inhibition, highlighting human dihydroorotate dehydrogenase (hDHODH), a rate-limiting enzyme in the de novo pathway, as a potential therapeutic target. MEDS433 is a best-in-class hDHODH inhibitor, that shows efficacy in vivo after oral administration but lacks efficient penetration of the blood-brain barrier (BBB), limiting its utility against CNS tumors. Its lipophilic analogue MEDS613 showed enhanced cellular potency, but its poor metabolic stability and rapid conversion to hydroxylated metabolites precluded its future clinical development. In this study, we aimed to design a novel BBB-permeable hDHODH inhibitor, capable of effectively targeting CNS-localized hDHODH. We began by identifying the metabolic soft spots present in the propyloxy side chain of MEDS613 using this information to develop a metabolically stable analogue, MEDS700 (compound 3, as named in the manuscript), that was shown to inhibit hDHODH in the low nanomolar range (IChDHODH 1.5 nM). Subsequently, MEDS700 was fully profiled, including detailed analysis of its crystallographic binding mode, pan-antitumor activities in cell-based assays and in vitro cytotoxicity on Peripheral Blood Mononuclear Cells (PBMC). An in vivo pharmacokinetic experiment demonstrated that MEDS700 was able to cross the blood-brain barrier, maintaining therapeutically relevant intracerebral concentrations for up to 24 h after oral administration. Our findings establish MEDS700 as a potent, safe, metabolically stable hDHODH inhibitor, indicating it as a promising candidate for the treatment of hard-to-reach brain tumors. - Source: PubMed
Publication date: 2026/04/27
Sainas StefanoVigato ChiaraCircosta PaolaZonfrillo ManuelaServidei TizianaAlberti MartaRescigno MartinaMiggiano RiccardoGaidano ValentinaVitale NicolettaPassoni AliceLanno AlessiaBuccinnà BarbaraPiccinini MarcoLorenzati MartinaGentile SerenaSferrazza GianlucaSgambato AlessandroSaglio GiuseppeGiorgis MartaBoschi DonatellaLolli Marco L - Schistosomiasis is a parasitic disease affecting millions worldwide, highlighting the urgent need for effective treatments. This study investigated a new potential site on dihydroorotate dehydrogenase (DHODH) and identified natural compounds as inhibitors from in silico and experimental techniques. Molecular docking and dynamics simulations revealed significant interactions between DHODH and -kaur-16-en-19-oic acid (3) and 15β-senecioil-oxi-ent-kaur-16-en-19-oic acid (4). The complex formed by compound 3 and the biological target showed the lowest free binding energy, indicating greater stability. Experimental assays indicated that compound 3 significantly reduced DHODH activity (40 ± 2% at 250 µM), while compound 4 had minimal effect (90 ± 1%). Structural analyses revealed that hydrophobic interactions at site 1 and conformational changes induced by compound 3 are crucial for effective enzyme inhibition. Therefore, from the computational and experimental approaches employed in this study, we were able to understand a possible mechanism related to the DHODH inhibition and the discovery of a potential bioactive compound against this important target related to schistosomiasis. - Source: PubMed
Publication date: 2026/05/08
de Angelo Rafaela Molinade Oliveira Almeida MichellEncide João Pedro PortilhoBarbosa HenriqueDe Sousa Daniel da Silvada Silva Aldineia PereiraMendes Marina SenaNonato Maria CristinaDa Silva Albérico Borges FerreiraLago João Henrique GhilardiHonorio Kathia Maria - Pyrimidine is required for the biosynthesis of DNA, RNA, glycoproteins, and phospholipids. Dihydroorotate dehydrogenase (DHODH) is a crucial flavin-dependent enzyme in mitochondria involved in the de novo pyrimidine synthesis and has been considered a significant drug target for diseases involving viral infections and parasitic diseases. Moreover, it has gained attention as a promising target for cancer treatment in recent years. This review introduces the structural and biochemical properties of DHODH and elaborates on its role in mitochondrial energy metabolism and ferroptosis. It summarizes the role of DHODH in cancer occurrence and development, as well as the in vivo effects and related regulatory mechanisms of DHODH inhibition. Moreover, it systematically discusses the latest developments in drug development based on the selective inhibition of DHODH, and introduces the therapeutic potential of DHODH inhibitors in cancer, bacterial and viral infections, and immune disorders. - Source: PubMed
Publication date: 2026/04/29
Guan XiaoyingLi JinchunGuan XiaoliHao CuirongZhang YajieYan Hong - This study aimed to create innovative transfersomes (TRFs) consisting of a lipid blend and a chemical permeation enhancer for efficient transdermal delivery of leflunomide (LFN). Leflunomide, a dihydroorotate dehydrogenase inhibitor, is mainly used to manage rheumatoid arthritis (RA). Oral consumption of LFN for RA can lead to adverse systemic effects; hence, local application is advisable. To develop topical dosage form of LFN, transfersomes with improved skin permeation capabilities were fabricated. The vesicle diameter of LFN-TRF was determined to be 181.2 ± 2.17 nm, zeta potential of - 29.2 ± 0.06 mV, PDI of 0.259 ± 0.006, and encapsulation percentage (EE) of 86.5 ± 3.45%. Notably, the developed formulation exhibited slow and sustained release of up to 78.87% of LFN over 24 h. The drug permeation from the nanocarriers was found to be around 67% for the LFN-TRF-gel and 55.33% for the LFN-gel. Skin irritation assessments indicated no signs of irritation, inflammation, or toxicity, affirming the formulation's nontoxic and biocompatible characteristics. In vivo studies demonstrated higher anti-inflammatory and anti-arthritic activity than conventional gel. In summary, this study presents a viable alternative for formulating effective topical LFN preparation using transfersomes. - Source: PubMed
Publication date: 2026/05/01
Moravkar KailasThakare RutujaKumawat VivekSapkal SandipChalikwar ShaileshNirbhavane Pradip