基抑制剂ABL001可以对BCR-ABL1进行双重向
Andrew A Wylie1, Joseph Schoepfer2, Wolfgang Jahnke2
1Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA.
Nature
|March 23, 2017
概括
ABL001 (阿西米尼布) 是一种用于慢性髓性白血病 (CML) 的新型全抑制剂. 结合ABL001和尼罗丁尼的治疗消除了小鼠的CML瘤,显示出长期控制疾病的潜力.
科学领域:
- 癌症学
- 分子生物学
- 药理学
背景情况:
- 慢性髓性白血病 (CML) 是由BCR-ABL1瘤蛋白驱动的.
- 激酶抑制剂改善了CML的结果,但耐药性仍然是一个挑战.
- 了解新药机制对于推进CML治疗至关重要.
研究的目的:
- 描述ABL001 (阿西米尼布),一种新型全性ABL1抑制剂.
- 在临床前CML模型中研究ABL001单独或与尼洛替尼结合的疗效.
主要方法:
- ABL001与ABL1的myristoyl口袋的结合的特征
- 评估细胞功效和耐药性突变特征.
- 在CML异种移植瘤的小鼠中使用单剂和组合疗法的临床前研究.
主要成果:
- ABL001与米里斯囊结合,诱导非活跃的ABL1形态.
- ABL001和尼洛丁尼表现出明显的抗性突变模式.
- 结合ABL001和尼罗丁尼,在小鼠中实现了完全的疾病控制和瘤根除,没有复发.
结论:
- ABL001代表了针对myristoyl口袋的CML的独特治疗方法.
- 使用ABL001和尼洛替尼的联合治疗对CML具有强大的临床前疗效.
- 这种组合有望在CML患者中克服耐药性并实现持久反应.
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