Therapeutic agents brequinar sodium and leflunomide (Arava) work by binding in a hydrophobic tunnel formed by a highly variable N-terminus of family 2 dihydroorotate dehydrogenase (DHODH). The X-ray crystallographic structure of an analog of brequinar bound to human DHODH was determined. In silico screening of a library of compounds suggested another subset of brequinar analogs that do not inhibit human DHODH as potentially effective inhibitors of Plasmodium falciparum DHODH.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2005.12.029 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A human metabolic map of pharmacological perturbations reveals drug modes of action.
Nat Biotechnol
January 2025
Department of Biomedicine, University of Basel, Basel, Switzerland.
Understanding a small molecule's mode of action (MoA) is essential to guide the selection, optimization and clinical development of lead compounds. In this study, we used high-throughput non-targeted metabolomics to profile changes in 2,269 putative metabolites induced by 1,520 drugs in A549 lung cancer cells. Although only 26% of the drugs inhibited cell growth, 86% caused intracellular metabolic changes, which were largely conserved in two additional cancer cell lines.
View Article and Find Full Text PDFQuinoline and quinolone carboxamides: A review of anticancer activity with detailed structure-activity relationship analysis.
Mol Divers
January 2025
Department of Chemistry, National Institute of Technology Calicut, Kozhikode, 673601, Kerala, India.
Quinoline is a highly privileged scaffold with significant pharmacological potential. Introducing a carbonyl group into the quinoline ring generates a quinolone ring, which exhibits promising biological properties. Incorporating a carboxamide linkage at different positions within the quinoline and quinolone frameworks has proven an effective strategy for enhancing pharmacological properties, particularly anticancer potency.
View Article and Find Full Text PDFExploring the antifungal potential of -derived stilbenoids and cannabinoids against novel targets through protein interaction profiling.
Front Chem
January 2025
Department of Surgery, Pirogov Russian National Research Medical University, Moscow, Russia.
Cannabinoid and stilbenoid compounds derived from were screened against eight specific fungal protein targets to identify potential antifungal agents. The proteins investigated included Glycosylphosphatidylinositol (GPI), Enolase, Mannitol-2-dehydrogenase, GMP synthase, Dihydroorotate dehydrogenase (DHODH), Heat shock protein 90 homolog (Hsp90), Chitin Synthase 2 (CaChs2), and Mannitol-1-phosphate 5-dehydrogenase (M1P5DH), all of which play crucial roles in fungal survival and pathogenicity. This research evaluates the binding affinities and interaction profiles of selected cannabinoids and stilbenoids with these eight proteins using molecular docking and molecular dynamics simulations.
View Article and Find Full Text PDFVidofludimus 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 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!