Abstract

Dimethyl itaconate (DMI) is an analog of dimethyl fumarate (DMF), an approved NF-E2-related Factor 2 (Nrf2) activator for multiple sclerosis. This study evaluated the potential of DMI as an anti-inflammatory agent by comparing DMI with DMF in electrophilicity, Nrf2 activation, and anti-inflammation in vitro. The results showed that DMI was less electrophilic but better at inducing a durable activation of Nrf2 when compared with DMF. However, DMI demonstrated poor anti-inflammatory effects in Jurkat cells, bone marrow-derived dendritic cells, and RAW264.7 cells. Our study suggested that DMI was a potent electrophilic Nrf2 activator but was probably not a promising anti-inflammatory agent.

摘要

衣康酸二甲酯 (DMI) 是富马酸二甲酯 (DMF) 的类似物，后者是一种获批用于多发性硬化症的 NF-E2 相关因子 2 (Nrf2) 激活剂。本研究通过比较 DMI 与 DMF在体外的亲电性、Nrf2 激活和抗炎作用来评估 DMI 作为抗炎剂的潜力。结果表明，与 DMF 相比，DMI 的亲电性较低，但在诱导 Nrf2 的持久激活方面更好。然而，DMI 在 Jurkat 细胞、骨髓来源的树突状细胞和 RAW264.7 细胞中表现出较差的抗炎作用。我们的研究表明，DMI 是一种有效的亲电 Nrf2 激活剂，但可能不是一种有前途的抗炎剂。