TAK-828F，一种新型口服 RORγt 反向激动剂，在慢性实验性自身免疫性脑脊髓炎模型小鼠中的药效学评价。
Pharmacological evaluation of TAK-828F, a novel orally available RORγt inverse agonist, on murine chronic experimental autoimmune encephalomyelitis model.
机构信息
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan; Pharmaceutical Sciences, Takeda Pharmaceutical Company, Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan; Axcelead Drug Discovery Partners, Inc., 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
出版信息
J Neuroimmunol. 2019 Oct 15;335:577016. doi: 10.1016/j.jneuroim.2019.577016. Epub 2019 Jul 25.
We investigated the potency of TAK-828F, a RORγt inverse agonist, in murine experimental autoimmune encephalomyelitis (EAE) model. TAK-828F inhibited the differentiation of Th17 and Th1/17 cells in inguinal lymph node. Increase of these cells in central nervous system (CNS) was also inhibited by TAK-828F. Prophylactic and therapeutic treatments of TAK-828F were efficacious in the model. Plasma concentration of TAK-828F was higher than that in CNS. These results indicate that TAK-828F mainly acts at peripheral and results in the reduction of Th17- and Th1/17-dependent inflammation in CNS. Blocking RORγt may be a promising strategy for treatment of multiple sclerosis.
我们研究了 RORγt 反向激动剂 TAK-828F 在实验性自身免疫性脑脊髓炎（EAE）模型中的效力。TAK-828F 抑制腹股沟淋巴结中 Th17 和 Th1/17 细胞的分化。TAK-828F 还抑制了这些细胞在中枢神经系统（CNS）中的增加。TAK-828F 的预防和治疗在该模型中是有效的。TAK-828F 的血浆浓度高于 CNS 中的浓度。这些结果表明，TAK-828F 主要在周围起作用，并导致 CNS 中 Th17 和 Th1/17 依赖性炎症的减少。阻断 RORγt 可能是多发性硬化症治疗的一种有前途的策略。
Zotero 插件