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KRAS抑制剂的发展历程

2024-01-08
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经过多年的努力,科学家们在针对几种恶性肿瘤的KRAS突变方面已经取得了多向进展:

After decades of efforts, scientists have made progress into targeting KRAS mutations in several malignancies.

在1967年, Ha-Ras 和 Ki-Ras逆转录病毒转化基因被发现,它们对应的人类RAS家族HRAS和KRAS于1982年被发现.

In 1967, Ha-Ras and Ki-Ras retroviral transforming genes were discovered.Their human counterparts,Ha-Ras and Ki-Ras ,were discovered in 1982.

KRAS 与肺癌的关系于1984年被首次描述,这些年KRAS 突变在肺癌中已经有多项进展。突变的KRAS被持续性激活,并导致持续的下游信号传导和肿瘤发生。

The relationship between KRAS and lung cancer was described in 1984,KRAS mutation in lung cancer has progressed.Mutant KRAS is constitutively activated and leads to persistent downstream signalling and oncogenesis.

在2013年随着对KRAS生物学的了解加深和药物设计技术的更新,科学家们在GDP结合的突变型KRAS G12C 蛋白中发现了半胱氨酸药物结合袋。

In 2013 improved understanding of KRAS biology and newer drug designing technologies led to crucial discovery of a cysteins drug binding pocket in GDP-bound mutant KRAS G12C  protein.

在2021年,科学家们成功开发出阻断突变型KRAS G12C 的共价抑制剂。2021年5月,Sotorasib获得FDA批准,用于治疗KRAS G12C突变的NSCLC,这是第一个获批的KRAS G12C抑制剂,目前还有更多药物正在研发中。

In 2021,covalent inhibitors that block mutant KRAS G12C were successfully developed.In May 2021 the US FDA granted accelerated approval to Sotorasib(1st KRAS G12C inhibitor),for the treatment of adults with advanced NSCLC with KRAS G12C mutation.Sotorasib was the first KRAS G12C inhibitor to be approved,with several more in the pipeline。

更多“KRAS靶点”相关内容推荐

KRAS新药研发平台

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KRAS的信号通路

z6尊龙助力信诺维抗肿瘤1类新药XNW14010(小分子KRAS G12C蛋白共价结合抑制剂)获批临床

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