Dimethyl fumarate, a two‐edged drug: Current status and future directions
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- Nathaniel Edward Bennett Saidu
- Department of Development, Reproduction and Cancer, Paris Descartes University, Sorbonne Paris Cité, INSERM U1016, Cochin Institute, CARPEM Paris France
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- Niloufar Kavian
- Department of Development, Reproduction and Cancer, Paris Descartes University, Sorbonne Paris Cité, INSERM U1016, Cochin Institute, CARPEM Paris France
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- Karen Leroy
- Department of Development, Reproduction and Cancer, Paris Descartes University, Sorbonne Paris Cité, INSERM U1016, Cochin Institute, CARPEM Paris France
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- Claus Jacob
- Division of Bioorganic Chemistry University of Saarland Saarbruecken Germany
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- Carole Nicco
- Department of Development, Reproduction and Cancer, Paris Descartes University, Sorbonne Paris Cité, INSERM U1016, Cochin Institute, CARPEM Paris France
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- Frédéric Batteux
- Department of Development, Reproduction and Cancer, Paris Descartes University, Sorbonne Paris Cité, INSERM U1016, Cochin Institute, CARPEM Paris France
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- Jérôme Alexandre
- Department of Development, Reproduction and Cancer, Paris Descartes University, Sorbonne Paris Cité, INSERM U1016, Cochin Institute, CARPEM Paris France
Description
<jats:title>Abstract</jats:title><jats:p>Dimethyl fumarate (DMF) is a fumaric acid ester registered for the treatment of relapsing‐remitting multiple sclerosis (RRMS). It induces protein succination leading to inactivation of cysteine‐rich proteins. It was first shown to possess cytoprotective and antioxidant effects in noncancer models, which appeared related to the induction of the nuclear factor erythroid 2 (NF‐E2)–related factor 2 (NRF2) pathway. DMF also displays antitumor activity in several cellular and mice models. Recently, we showed that the anticancer mechanism of DMF is dose‐dependent and is paradoxically related to the decrease in the nuclear translocation of NRF2. Some other studies performed indicate also the potential role of DMF in cancers, which are dependent on the NRF2 antioxidant and cellular detoxification program, such as KRAS‐mutated lung adenocarcinoma. It, however, seems that DMF has multiple biological effects as it has been shown to also inhibit the transcription factor nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), thus blocking downstream targets that may be involved in the development and progression of inflammatory cascades leading to various disease processes, including tumors, lymphomas, diabetic retinopathy, arthritis, and psoriasis. Herein, we present the current status and future directions of the use of DMF in various diseases models with particular emphases on its targeting of specific intracellular signal transduction cascades in cancer; to shed some light on its possible mode of action.</jats:p>
Journal
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- Medicinal Research Reviews
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Medicinal Research Reviews 39 (5), 1923-1952, 2019-02-12
Wiley
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Details 詳細情報について
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- CRID
- 1360011145223044608
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- ISSN
- 10981128
- 01986325
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- Data Source
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- Crossref