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.

中文翻译：

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富马酸二甲酯，一种两边缘药物：现状和未来方向。

富马酸二甲酯（DMF）是已注册用于治疗复发缓解型多发性硬化症（RRMS）的富马酸酯。它诱导蛋白质琥珀酸化，导致富含半胱氨酸的蛋白质失活。在非癌症模型中，它首先被证明具有细胞保护和抗氧化作用，这似乎与诱导核因子红系2（NF-E2）-相关因子2（NRF2）通路有关。DMF在几种细胞和小鼠模型中也显示出抗肿瘤活性。最近，我们证明了DMF的抗癌机制是剂量依赖性的，并且与NRF2核易位的减少自相矛盾。进行的其他一些研究表明，DMF在癌症中的潜在作用也取决于NRF2抗氧化剂和细胞排毒程序，例如KRAS突变的肺腺癌。它，但是，DMF似乎具有多种生物学作用，因为它也显示出抑制激活的B细胞（NF-κB）的转录因子核因子轻链增强子，从而阻断了可能参与发育的下游靶标炎症级联反应的进展，导致各种疾病的发生，包括肿瘤，淋巴瘤，糖尿病性视网膜病，关节炎和牛皮癣。在本文中，我们介绍了DMF在各种疾病模型中的使用现状和未来方向，特别是针对其针对癌症中特定细胞内信号转导级联的靶向。阐明其可能的作用方式。DMF似乎具有多种生物学作用，因为它也显示出抑制激活的B细胞的转录因子核因子κ轻链增强子（NF-κB），从而阻断了可能参与发育和进程的下游靶标导致各种疾病过程的炎症级联反应，包括肿瘤，淋巴瘤，糖尿病性视网膜病，关节炎和牛皮癣。在本文中，我们介绍了DMF在各种疾病模型中的使用现状和未来方向，特别是针对其针对癌症中特定细胞内信号转导级联的靶向。阐明其可能的作用方式。DMF似乎具有多种生物学效应，因为它也显示出抑制活化B细胞的转录因子核因子κ轻链增强子（NF-κB），从而阻断了可能参与发育和进程的下游靶标导致各种疾病过程的炎症级联反应，包括肿瘤，淋巴瘤，糖尿病性视网膜病，关节炎和牛皮癣。在本文中，我们介绍了DMF在各种疾病模型中的使用现状和未来方向，特别是针对其针对癌症中特定细胞内信号转导级联的靶向。阐明其可能的作用方式。淋巴瘤，糖尿病性视网膜病，关节炎和牛皮癣。在本文中，我们介绍了DMF在各种疾病模型中的使用现状和未来方向，特别是针对其针对癌症中特定细胞内信号转导级联的靶向。阐明其可能的作用方式。淋巴瘤，糖尿病性视网膜病，关节炎和牛皮癣。在本文中，我们介绍了DMF在各种疾病模型中的使用现状和未来方向，特别是针对其针对癌症中特定细胞内信号转导级联的靶向。阐明其可能的作用方式。