Arthritis Res Ther. 2011 Aug 12;13(4):122. doi: 10.1186/ar3392.
High expression of folate receptors is characteristic for the effector cell population of synovial macrophages in synovial inflammation. A new drug conjugate, EC0746, targets the folate inhibitor aminopterin to folate receptors. In vitro studies show that this conjugate acts antiproliferatively and inhibits cytokine production by macrophage cell lines. Moreover, it shows strong anti-arthritic effects in the rat model of adjuvant-induced arthritis in vivo. Toxicity of aminopterin was reduced 40-fold by using equimolar doses of the drug conjugate. In conclusion, this new treatment approach has the potential to further improve the most successful principle of folate inhibition in the treatment of arthritis.
高表达的叶酸受体是滑膜炎症中滑膜巨噬细胞效应细胞群的特征。一种新的药物偶联物 EC0746 将叶酸抑制剂氨甲喋呤靶向叶酸受体。体外研究表明,该偶联物具有抗增殖作用,并抑制巨噬细胞系细胞因子的产生。此外,它在体内佐剂诱导关节炎大鼠模型中表现出强烈的抗关节炎作用。使用等摩尔剂量的药物偶联物,氨甲喋呤的毒性降低了 40 倍。总之,这种新的治疗方法有可能进一步改进叶酸抑制在关节炎治疗中最成功的原则。