Abstract
Background: Human dihydroorotate dehydrogenase (hDHODH, EC 1.3.5.2), a flavindependent mitochondrial enzyme involved in de novo pyrimidine biosynthesis, is a validated therapeutic target for the treatment of autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis. However, human DHODH inhibitors have also been investigated as treatment for cancer, parasite infections (i.e. malaria) and viruses as well as in the agrochemicals industry.
Objective: An overview of current knowledge of hDHODH inhibitors and their potential uses in diseases where hDHODH is involved.
Method: This review focuses on recent advances in the development and application of hDHODH inhibitors, specifically covering the patent field, starting from a brief description of enzyme topography and of the strategies usually followed in designing its selective inhibitors.
Results: The most important and well-described novelty is the fact that the discovery, in the autumn of 2016, that hDHODH inhibitors are able to induce in vivo myeloid differentiation has led to the possibility of developing novel hDHODH based treatments for Acute Myelogenous Leukemia (AML).
Conclusion: The review will describe a variety of specific inhibitor classes and conclude on recent and future therapeutic perspectives for this target.
Keywords: Autoimmune diseases, brequinar, cancer, dihydroorotate dehydrogenase (DHODH), inhibitors, leflunomide, leukemia, melanoma.
Recent Patents on Anti-Cancer Drug Discovery
Title:Use of human Dihydroorotate Dehydrogenase (hDHODH) Inhibitors in Autoimmune Diseases and New Perspectives in Cancer Therapy
Volume: 13 Issue: 1
Author(s): Marco L. Lolli, Stefano Sainas, Agnese C. Pippione, Marta Giorgis, Donatella Boschi and Franco Dosio*
Affiliation:
- Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin,Italy
Keywords: Autoimmune diseases, brequinar, cancer, dihydroorotate dehydrogenase (DHODH), inhibitors, leflunomide, leukemia, melanoma.
Abstract: Background: Human dihydroorotate dehydrogenase (hDHODH, EC 1.3.5.2), a flavindependent mitochondrial enzyme involved in de novo pyrimidine biosynthesis, is a validated therapeutic target for the treatment of autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis. However, human DHODH inhibitors have also been investigated as treatment for cancer, parasite infections (i.e. malaria) and viruses as well as in the agrochemicals industry.
Objective: An overview of current knowledge of hDHODH inhibitors and their potential uses in diseases where hDHODH is involved.
Method: This review focuses on recent advances in the development and application of hDHODH inhibitors, specifically covering the patent field, starting from a brief description of enzyme topography and of the strategies usually followed in designing its selective inhibitors.
Results: The most important and well-described novelty is the fact that the discovery, in the autumn of 2016, that hDHODH inhibitors are able to induce in vivo myeloid differentiation has led to the possibility of developing novel hDHODH based treatments for Acute Myelogenous Leukemia (AML).
Conclusion: The review will describe a variety of specific inhibitor classes and conclude on recent and future therapeutic perspectives for this target.
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Lolli L. Marco, Sainas Stefano , Pippione C. Agnese , Giorgis Marta , Boschi Donatella and Dosio Franco *, Use of human Dihydroorotate Dehydrogenase (hDHODH) Inhibitors in Autoimmune Diseases and New Perspectives in Cancer Therapy, Recent Patents on Anti-Cancer Drug Discovery 2018; 13 (1) . https://dx.doi.org/10.2174/1574892812666171108124218
DOI https://dx.doi.org/10.2174/1574892812666171108124218 |
Print ISSN 1574-8928 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3970 |
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In recent years, traditional cancer treatments, such as surgery, chemotherapy, and radiation treatment, etc., may damage the pathological tissue and normal cells. The ideal tumor treatment should be noninvasive, eliminating the primary tumor, making the body produce systemic tumor-specific immunity, eliminating metastases, and having less /no side effects. Recent Patents ...read more
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