ディプロボキム: トール型受容体アゴニストの新種で,極めて強力である

Matthew D Morin¹, Ying Wang², Brian T Jones¹

¹Department of Chemistry and the Skaggs Institute of Chemical Biology , The Scripps Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 United States.

Journal of the American Chemical Society

|October 2, 2018

まとめ

研究者らは,トール型受容体 (TLR) -2の二分化を誘発することで免疫系を活性化する新しい小分子であるディプロキムを発見した. これらの強力な化合物は免疫反応の修正剤として有望な効果を示しています

科学分野:

免疫学
薬剤化学
薬物の発見

背景:

免疫反応の刺激は治療的介入に不可欠です
新しい免疫反応活性化剤の発見は継続的な課題です
トール型受容体 (TLR) は,先天的な免疫の重要な調節体です.

研究の目的:

免疫反応活性化剤の新種を発見し特徴づけること
トール型受容体 (TLR) のシグナリングを調節する化合物を特定する.
強力で合成可能なTLRアゴニストを開発する.

主な方法:

受容体二分化のために設計された化合物ライブラリの高通量スクリーニング.
分化したTHP-1骨髄細胞からのTNF-α放出を測定する機能的測定法.
化合物の効能を最適化するための構造-活性関係研究

主要な成果:

免疫反応活性化剤の新種であるディプロボキムの発見
ディプロボシムはTLR1 (TLR1/ TLR2アゴニスト) との細胞表面トール型受容体 (TLR) - 2二酸化を誘導する.
最も強力な化合物はピコモラ濃度で活性化されます.

結論:

Diprovocimsは,ユニークな構造を持つ小分子TLR1/TLR2アゴニストの新しいクラスを表しています.
これらの化合物は強力で人体とネズミの両方のシステムで活性化します
ディプロボシムは,既知のTLRアゴニストと比較して優れた効能を示し,治療的可能性を示しています.

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