AI Article Synopsis
Article Abstract
The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical studies in rheumatoid arthritis are in progress.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm9604437 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Vidofludimus Calcium in Patients with Moderate-to-Severe Ulcerative Colitis: A Randomized, Placebo-Controlled, Phase 2 Trial.
Clin Transl Gastroenterol
January 2025
Immunic AG, Lochhamer Schlag 21, 82166 Gräfelfing, Germany.
Introduction: Vidofludimus calcium (VidoCa) is a dihydroorotate dehydrogenase (DHODH) inhibitor that demonstrated efficacy in immune-related diseases. This study assessed the safety and efficacy of VidoCa in patients with active ulcerative colitis (UC).
Methods: This placebo-controlled, phase 2 trial randomized adults with moderate-severe UC to receive once-daily VidoCa (10, 30, or 45 mg) or placebo for 10 weeks (induction); patients with symptomatic remission were re-randomized to VidoCa 10, 30 mg, or placebo once-daily for an additional 40 weeks (maintenance).
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 PDFFerroptosis and PANoptosis under hypoxia pivoting on the crosstalk between DHODH and GPX4 in corneal epithelium.
Free Radic Biol Med
January 2025
Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:
Cell death under stress conditions like hypoxia, involves multiple interconnected pathways. In this study, a stable dihydroorotate dehydrogenase (DHODH) knockdown human corneal epithelial cell line was established to explore the regulation of hypoxic cell death, which was mitigated by various cell death inhibitors, particularly by a lipid peroxyl radical scavenger liproxstatin-1 (Lip-1), suggesting that hypoxic cell death involves crosstalk of ferroptosis and PANoptosis. We discovered that both DHODH and Glutathione peroxidase 4 (GPX4) protected cells from hypoxic death by inhibiting lipid peroxidation, mitochondrial reactive oxygen species (ROS) and maintaining mitochondrial membrane potential.
View Article and Find Full Text PDFCorrection: Vidofludimus inhibits porcine reproductive and respiratory syndrome virus infection by targeting dihydroorotate dehydrogenase.
Vet Res
December 2024
Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
Exploring the Venom Gland Transcriptome of and : De Novo Assembly and Analysis of Novel Toxic Proteins.
Toxins (Basel)
November 2024
Facultad de Ciencias Exactas y Naturales, Pontificia Universidad Católica del Ecuador, Quito 170525, Ecuador.
Previous proteomic studies of viperid venom revealed that it is mainly composed of metalloproteinases (SVMPs), serine proteinases (SVSPs), phospholipase A2 (PLA2), and C-type lectins (CTLs). However, other proteins appear in minor amounts that affect prey and need to be identified. This study aimed to identify novel toxic proteins in the venom gland transcriptome of and , using data from NCBI.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!