全身活性を持つアミドベンジミダゾールSTING受容体アゴニストの設計
Joshi M Ramanjulu1, G Scott Pesiridis2, Jingsong Yang3
1Pattern Recognition Receptor DPU, GlaxoSmithKline, Collegeville, PA, USA. joshi.m.ramanjulu@gsk.com.
Nature
|November 9, 2018
まとめ
研究者は新しい小分子STINGアゴニスト (diABZI) を発見し マウスの腫瘍を効果的に治療しました この非周期性ダイヌクレオチド化合物は全身の有効性を示し 癌の免疫療法における有望な新たな手段を提示しています
科学分野:
- 免疫学
- 薬理学について
- 腫瘍学
背景:
- インターフェロン遺伝子の刺激剤 (STING) は,DNAの先天的な免疫感知に不可欠です.
- STING 調節剤は,がん,感染症,ワクチン補助剤について研究されています.
- 現在のSTINGアゴニストは主に循環性ダイヌクレオチドで,全身的な適用は限られている.
研究 の 目的:
- 新型非周期性ダイヌクレオチド小分子STINGアゴニストの発見
- 癌治療のための全身的に効果的なSTINGアゴニストを開発する.
- STINGの結合と細胞機能の強化を目的として
主な方法:
- アミドベンジミダゾール (ABZI) ベースの化合物をリンクされたABZI (diABZI) にリンクする戦略を開発した.
- STINGと細胞活動に対するdiABZI結合親和性を評価した.
- 免疫能力のあるマウスの体内腫瘍に対するdiABZIの効果を評価した.
主要な成果:
- 新しい小分子のSTINGアゴニスト,ダイアブジを発見した. 周期性ダイヌクレオチドとは異なる.
- diABZIはSTINGへの結合が強化され,細胞機能が改善されました.
- マウスの体内投与は,既成の大腸腫瘍の完全かつ持続的な回復をもたらした.
結論:
- 新規のdiABZI STINGアゴニストは,確立した腫瘍に対して全身的に有効です.
- この発見は 免疫系を改変するがん治療の 重要な進歩を表しています
- 非周期性ダイヌクレオチドSTINGアゴニストは,がん治療における有望な新種の治療薬を提供します.
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