Details

Autor(en) / Beteiligte

• Nakamura, Yoshiki
• Igaki, Keiko
• Uga, Keiko
• Shibata, Akira
• Yamauchi, Hirofumi
• Yamasaki, Masashi
• Tsuchimori, Noboru

Titel

Pharmacological evaluation of TAK-828F, a novel orally available RORγt inverse agonist, on murine chronic experimental autoimmune encephalomyelitis model

Ist Teil von

• Journal of neuroimmunology, 2019-10, Vol.335, p.577016-577016, Article 577016

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •RORγt inverse agonist, TAK-828F, suppressed Th17 and Th1/17 cells in lymph node.•TAK-828F was prophylactically and therapeutically efficacious in murine EAE model.•Increase in Th17 and Th1/17 cell in CNS tissue was inhibited by TAK-828F treatment.•Plasma concentration of TAK-828F was higher than that in spinal cord of EAE mice.•TAK-828F acts at peripheral and results in the reduction of immune reaction in CNS.