薬剤の非活性成分が生物学的標的に及ぼす作用
Joshua Pottel1, Duncan Armstrong2, Ling Zou3
1Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA.
Science (New York, N.Y.)
|July 25, 2020
まとめ
多くの薬の副成分,または非活性成分は,予期せぬ生物学的活性を示します. この研究では25の in vitro 活性が発見され,潜在的な毒性が特定され,一部の補助物質が生理学的標的を積極的に調節することが明らかになった.
科学分野:
- 薬理学について
- 薬物の発見
- 毒理学について
背景:
- 副成分は,製薬剤の主要な成分であり,薬理学に影響を与える.
- 分子標的に対する補助物質の生物学的作用は,体系的に調査されていない.
研究 の 目的:
- 承認された補助物質が分子標的と結合する確率を計算する.
- 補助物質の in vitro および in vivo 活動を特定する.
- 補助剤による毒性の可能性を評価する.
主な方法:
- 補助物質と標的の結合確率の計算分析
- 濃度範囲におけるエキシピエントの活性に対する in vitro 試験.
- 細胞モデルのシステムレベルの毒性試験
- 選択されたエキシピエントの in vivo 暴露調査
主要な成果:
- 25の in vitro 補助物質の活性 (低ナノモラーから高マイクロモラー) を特定した.
- 臨床安全目標に対する109の追加の活動を発見した.
- 毒性を予測する指紋を 細胞モデルで5つ見つけた
- 特定の曝露レベルでのチメロサールおよびその代謝物の潜在的 in vivo 標的効能を観察した.
結論:
- ほとんどの補助剤は惰性ですが,多くの承認されたものは生理的に重要な標的を直接調節することができます.
- この発見は,エキシピエントの安全性と有効性のプロフィールを再評価することを必要としています.
- 薬剤開発には補助物質の薬理に関するさらなる研究が不可欠である.
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