farnesyltransferase阻害剤によるラス依存変異の選択的阻害
N E Kohl1, S D Mosser, S J deSolms
1Department of Cancer Research, Merck Research Laboratories, West Point, PA 19486.
Science (New York, N.Y.)
|June 25, 1993
まとめ
新型ファルネシルタンパク質トランスファーゼ (FPTase) 阻害剤L-731,734は,Rasオンコタンパク質の処理を選択的に阻害する. この薬剤候補は,Ras変異によって引き起こされるがんの治療に有望であることが示されています.
科学分野:
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- Rasオンコプロテインの活性化には,ファルネシル化が必要で,ファルネシルタンパク質移転酶 (FPTase) によって触媒化された改変である.
- FPTase阻害剤は,抗がん剤として,特にRas依存性腫瘍で研究されています.
研究 の 目的:
- 新型FPターゼ阻害剤L-731,734のRas処理と細胞変換を阻害する効果を評価する.
主な方法:
- L-731,735を選択的FPターゼ阻害剤として試験する.
- 前薬L-731,734.4を使用したv-ras変換細胞におけるRas処理の阻害
- v-ras,v-raf,およびv-mos変形細胞のための軟アガールにおけるコロニー形成の評価.
主要な成果:
- L-731,735 in vitroでFPTaseの有力かつ選択的阻害を示した.
- L-731,734は,v-ras変換細胞におけるRas処理を効果的に抑制しました.
- L-731,734 は,v-ras 変形細胞における軟アガール菌のコロニー形成を著しく減少させたが,v-raf または v-mos 変形細胞ではそうではない.
結論:
- 合成有機FPターゼ阻害剤は,Ras依存細胞変換を選択的に標的化することができます.
- L-731,734は,Ras駆動がんの標的型抗がん療法を開発するための有望な鉛化合物です.
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