On Dihydroorotate Dehydrogenases and Their Inhibitors and Uses

Munier-Lehmann, Hélène; Vidalain, Pierre-Olivier; Tangy, Frédéric; Janin, Yves L.

doi:10.1021/jm301848w

Cited by 236Biochemical and Molecular ResearchSynthesis and Characterization of Heterocyclic CompoundsSynthesis and biological activity

On Dihydroorotate Dehydrogenases and Their Inhibitors and Uses

Munier-Lehmann, Hélène, Vidalain, Pierre-Olivier, Tangy, Frédéric, Janin, Yves L.·2013·Journal of Medicinal Chemistry

DOI 10.1021/jm301848w

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Abstract

Proper nucleosides availability is crucial for the proliferation of living entities (eukaryotic cells, parasites, bacteria, and virus). Accordingly, the uses of inhibitors of the de novo nucleosides biosynthetic pathways have been investigated in the past. In the following we have focused on dihydroorotate dehydrogenase (DHODH), the fourth enzyme in the de novo pyrimidine nucleosides biosynthetic pathway. We first described the different types of enzyme in terms of sequence, structure, and biochemistry, including the reported bioassays. In a second part, the series of inhibitors of this enzyme along with a description of their potential or actual uses were reviewed. These inhibitors are indeed used in medicine to treat autoimmune diseases such as rheumatoid arthritis or multiple sclerosis (leflunomide and teriflunomide) and have been investigated in treatments of cancer, virus, and parasite infections (i.e., malaria) as well as in crop science.

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DHODH is required for de novo pyrimidine synthesis.
“The IMM enzyme dihydroorotate dehydrogenase (DHODH), which oxidizes dihydroorotate to orotate, is required for de novo pyrimidine synthesis.73”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [73]

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Human dihydroorotate dehydrogenase inhibitors, a novel approach for the treatment of autoimmune and inflammatory diseases
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A novel series of human dihydroorotate dehydrogenase inhibitors discovered by in vitro screening: inhibition activity and crystallographic binding mode
Zeng, T., Zuo, Z., Luo, Y., Zhao, Y., Yu, Y., & Chen, Q. (2019) · FEBS Open Bio · doi:10.1002/2211-5463.12658 · Cited by 12 · see citing works

Authors: Munier-Lehmann, H., Vidalain, P.-O., Tangy, F., & Janin, Y. L.
Affiliations: Institut Pasteur, Unité de Chimie et Biocatalyse, Département de Biologie Structurale et Chimie, 28 Rue du Dr. Roux, 75724 Paris Cedex 15, France
Centre National de la Recherche Scientifique (FR)
Corresponding author: Janin, Yves L.
ORCID: Vidalain, Pierre-Olivier
Tangy, Frédéric
Janin, Yves L.
Venue: Journal of Medicinal Chemistry
Publisher: American Chemical Society (ACS)
Published: 2013-03-20
Volume: 56
Issue: 8
Pages: 3148-3167
ISSN: 0022-2623 (ISSN-L)
1520-4804
DOI: 10.1021/jm301848w
OpenAlex: W2312482418
Cited by: 209
References: 275
Citations by year: 2026: 15 · 2025: 13 · 2024: 12 · 2023: 22 · 2022: 20 · 2021: 17 · 2020: 20 · 2019: 18 · 2018: 17 · 2017: 16 · 2016: 13 · 2015: 15 · 2014: 5 · 2013: 6
FWCI: 1.41
Type: journal article
Language: en
Open access: closed
Locations: Journal of Medicinal Chemistry (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Physical Sciences › Chemistry › Organic Chemistry › Synthesis and Characterization of Heterocyclic Compounds
Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Keywords: dihydroorotate dehydrogenase, DHODH inhibitors, leflunomide, teriflunomide, rheumatoid arthritis, multiple sclerosis, cancer therapy, antiviral agents, antimalarial drugs, crop protection
MeSH terms: Dihydroorotate Dehydrogenase, Animals, Bacteria, Coccidia, Coccidiostats, Enzyme Inhibitors, Humans, Oxidoreductases Acting on CH-CH Group Donors

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On Dihydroorotate Dehydrogenases and Their Inhibitors and Uses

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