アルセノプラチン-1は,ダブル・ファルマコフォア抗がん剤である
Đenana Miodragović1,2, Antonello Merlino3, Elden P Swindell1
1Chemistry of Life Processes Institute , Northwestern University , 2145 Sheridan Road , Evanston , Illinois 60208 , United States.
Journal of the American Chemical Society
|April 4, 2019
まとめ
新しい抗がん剤であるアルセノプラチン-1は,その原薬と比較して,様々ながん細胞系に対する優れた活性を示しています. この化合物は プラチナとヒ素の両方を 癌細胞に効果的に送って 固体腫瘍を治療する可能性を秘めています
科学分野:
- 薬剤化学
- 癌 生物学
- 薬物の発見
背景:
- アルゼンプラチンはシスプラチンと三酸化アルゼンチンを組み合わせて,新しい抗がん剤を形成します.
- 三酸化アルゼンチンは血液がんに有効ですが,迅速なクリアランスのために固体腫瘍に限られています.
- アルセノプラチン-1 (AP-1) は,このクラスの最初の化合物であり,強化された活性を示しています.
研究 の 目的:
- NCI-60ヒト腫瘍細胞系に対するアルセノプラチン-1 (AP-1) の抗癌活性を評価する.
- タンパク質とDNAとの生物学的相互作用を調査する.
- プラチナとヒ素の作用と発散の仕組みを理解する.
主な方法:
- NCI-60 がん細胞ラインのAP-1 活性に対するスクリーニング
- モデルタンパク質に結合するAP-1の構造研究
- 時間の経過におけるPt:As比を含む,AP-1とDNAの相互作用の分析.
主要な成果:
- AP- 1は,テストされたほとんどの細胞系において,シスプラチンと三酸化アルゼンチンに比べて優れた抗癌活性を示した.
- 構造の研究では,プラチナがタンパク質のHis残留物と結合し,Pt-As結合を保持することが示された.
- AP-1は細胞に入り,最初はPt-As結合でDNAを結合し,後にアルセンの分子を放出しました.
結論:
- Arsenoplatin- 1は,様々ながんの治療において,その原薬よりも優れた抗がん性を持っています.
- この化合物が最初はPt-As結合を保持し,その後はアルセニクを放出する能力は,二重配送メカニズムを示唆する.
- AP-1はプラチナとアルゼンチンの両種を投与することで 血性腫瘍と固体腫瘍の両方の治療に有望です
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