dihydroorotate dehydrogenase (quinone)

Target id: 2604

Nomenclature: dihydroorotate dehydrogenase (quinone)

Family: Nucleoside synthesis and metabolism, 1.-.-.- Oxidoreductases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     dihydroorotate dehydrogenase (quinone) has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 395 16q22.2 DHODH dihydroorotate dehydrogenase (quinone)
Mouse - 395 8 D3 Dhodh dihydroorotate dehydrogenase
Rat - 395 19q12 Dhodh dihydroorotate dehydrogenase (quinone)
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  High resolution crystal structure of human dihydroorotate dehydrogenase bound with 4-quinoline carboxylic acid analog
PDB Id:  4IGH
Resolution:  1.3Å
Species:  Human
References:  1
Enzyme Reaction
EC Number: 1.3.5.2

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
teriflunomide Hs Inhibition 7.5 pKi 2
pKi 7.5 (Ki 3x10-8 M) [2]
leflunomide Hs Inhibition 4.9 pKi 4
pKi 4.9 (Ki 1.3x10-5 M) [4]
Immunopharmacology Comments
Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine nucleosides biosynthetic pathway. DHODH inhibitors are used clinically to treat autoimmune diseases such as rheumatoid arthritis or multiple sclerosis (leflunomide and teriflunomide) [3].
Clinically-Relevant Mutations and Pathophysiology
Disease:  Postaxial acrofacial dysostosis
Synonyms: Miller syndrome
OMIM: 263750
Orphanet: ORPHA246
General Comments
Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine nucleosides biosynthetic pathway. DHODH inhibitors are used clinically to treat autoimmune diseases such as rheumatoid arthritis or multiple sclerosis (leflunomide and teriflunomide respectively) and have been investigated in oncology, virology, and parasitology (e.g. malaria) [3]. More information about Plasmodium falciparum DHODH (gene symbol PFF0160c for P. falciparum strain 3D7) as an anti-malarial drug target is contained in our evolving Anti-infective targets family.

References

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1. Das P, Deng X, Zhang L, Roth MG, Fontoura BM, Phillips MA, De Brabander JK. (2013) SAR Based Optimization of a 4-Quinoline Carboxylic Acid Analog with Potent Anti-Viral Activity. ACS Med Chem Lett4 (6): 517-521. [PMID:23930152]

2. Heikkilä T, Ramsey C, Davies M, Galtier C, Stead AM, Johnson AP, Fishwick CW, Boa AN, McConkey GA. (2007) Design and synthesis of potent inhibitors of the malaria parasite dihydroorotate dehydrogenase. J. Med. Chem.50 (2): 186-91. [PMID:17228860]

3. Munier-Lehmann H, Vidalain PO, Tangy F, Janin YL. (2013) On dihydroorotate dehydrogenases and their inhibitors and uses. J. Med. Chem.56 (8): 3148-67. [PMID:23452331]

4. Papageorgiou C, Albert R, Floersheim P, Lemaire M, Bitch F, Weber HP, Andersen E, Hungerford V, Schreier MH. (1998) Pyrazole bioisosteres of leflunomide as B-cell immunosuppressants for xenotransplantation and chronic rejection: scope and limitations. J. Med. Chem.41 (18): 3530-8. [PMID:9719606]

How to cite this page

1.-.-.- Oxidoreductases: dihydroorotate dehydrogenase (quinone). Last modified on 17/08/2017. Accessed on 12/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2604.