臨床用キナーゼ薬のターゲット環境

Susan Klaeger^1,2,3, Stephanie Heinzlmeir^1,2,3, Mathias Wilhelm¹

¹Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), Freising, Germany.

Science (New York, N.Y.)

|December 2, 2017

まとめ

この研究では,化学プロテオミクスを用いて243のキナーゼ阻害剤の標的をマッピングし,新しい薬標的と非標的を明らかにしました. 発見は癌薬の発見と臨床的意思決定を助け,潜在的な治療的応用を特定します.

科学分野:

生物化学
薬理学について
腫瘍学

背景:

キナーゼ阻害剤は重要ながん治療薬ですが,多剤薬学では標的の解体が必要になります.
薬の標的を理解することは作用のメカニズムを明らかにし治療戦略を最適化するために不可欠です

研究の目的:

化学プロテオミクスを用いて臨床的に評価されたキナーゼ薬のターゲットスペクトルを包括的に分析する.
既存のキナーゼ阻害剤の新たな標的,非標的および潜在的な治療用途を特定する.
薬に影響される経路を精製し,反応マーカーを特定するために,フォスフォプロテオミクデータを統合する.

主な方法:

化学プロテオミクスは,243のキナーゼ阻害剤のターゲットエンゲージメントをプロファイルするために使用されました.
薬剤誘発経路調節を評価するために,フォスフォプロテオミック分析を統合した.
SIK2 阻害,MELK ターゲティング,カボザンチニブの再利用など,事例研究で翻訳的価値が示されました.

主要な成果:

確立されたキナーゼ阻害剤の未知の標的が特定されました.
総合的な視点から

結論:

このプロテオミクスのリソースは,キナーゼ阻害剤のポリファーマコロジーに関する貴重な洞察を提供します.
この発見は基礎研究,臨床応用,がん治療薬の開発に役立つ.
データ統合は,特定の腫瘍性変異に対する組み合わせ治療と薬物の再利用を助ける.

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