The novel anti-inflammatory drug development complementing with glucocorticoid

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08472
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Hosoya Tadashi 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (60737104)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: NFκB / 関節炎モデル / 急性肝炎モデル

Outline of Final Research Achievements

We investigated the efficacy of the newly identified compound in several inflammatory animal models. It was dissolved in 20% Sulfobutylether-β-Cyclodextrin (SBE-β-CD), reached its peak concentration after 15 minutes post-intraperitoneal administration, and decreased to approximately 5% after 24 hours.
In a hepatitis model, it could suppress TNFα production and extend survival time, although it did not completely inhibit liver damage. In acute and chronic arthritis models, it suppressed bone and cartilage destruction and inflammatory cell infiltration. It also demonstrated the inhibition of antigen-dependent activation of immune cells and a reduction in dendritic cells in the lymph nodes in the chronic arthritis model.

Free Research Field

膠原病・リウマチ学分野

Academic Significance and Societal Importance of the Research Achievements

リウマチ性疾患をはじめとした炎症性疾患の治療には新規の抗炎症薬が求められている。本化合物は炎症を誘導する主要な転写因子NFκBの阻害活性をもつ物質として、大規模化合物ライブラリーからスクリーニングによって見出されたが、実際に複数の炎症モデルで有効性を示した。今後、本化合物が有する炎症抑制のメカニズムについてのさらなる解析を行い、薬剤開発のステップを進めていく。