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ASC:新型药物杀灭癌细胞无毒更有效

2017-04-26 枫丹白露 medicalxpress

普渡大学开发的药物化合物可有效靶向和抑制多种类型癌症的蛋白激酶酶和次级突变型。与常规药物相比,这些化合物是无毒的,可能消除不利的患者副作用。 普渡大学化学系教授和创新开发人员Hermin Sintim说:“蛋白激酶是参与细胞信号传导的一类重要蛋白质,它们调节细胞生长,死亡(细胞凋亡)和迁移等多种过程,人类细胞中有大约600种不同的蛋白激酶。由于参与细胞信号传导,蛋白激酶也参与癌症的形成。

普渡大学开发的药物化合物可有效靶向和抑制多种类型癌症的蛋白激酶酶和次级突变型。与常规药物相比,这些化合物是无毒的,可能消除不利的患者副作用。

 

普渡大学化学系教授和创新开发人员Hermin Sintim说:“蛋白激酶是参与细胞信号传导的一类重要蛋白质,它们调节细胞生长,死亡(细胞凋亡)和迁移等多种过程,人类细胞中有大约600种不同的蛋白激酶。由于参与细胞信号传导,蛋白激酶也参与癌症的形成。对于多种癌症,这些蛋白激酶变得突变,引起异常的细胞生长或者发生激酶复制,都不可避免地导致癌症。”
 
Sintim说,通常使用细胞毒性药物杀死癌细胞的常规方法构成了一些局限性。
 
他说:“典型的治疗方法集中在开发小分子以抑制激酶,这种方法与以前的药物化学家针对癌症的方式不同,这涉及使用细胞毒性药物,细胞毒性药物不分青红皂白地破坏DNA或细胞代谢设备或蛋白质,并且由于每个细胞都含有这些防线阻止毒品攻击身体的每一个细胞,而不是仅仅是癌症的细胞。顾名思义,细胞毒性药物是非常有毒的,可能会产生严重的不良副作用,如脱发,视力问题和神经系统问题。新方法后对于癌细胞突变,可能导致靶向治疗有更少的副作用。
 
Sintim开发了一种称为“azo-click-it/staple-it”的概念,可用于发现蛋白激酶抑制剂,其不仅靶向驱动癌症的初始激酶,而且靶向可能在初始抑制剂治疗后可重新出现的次要突变。研究结果最近发表在ACS药物化学通讯。
 
Sintim的治疗策略可以通过开发有希望的急性骨髓性白血病(AML)药物类来证明。
 
辛蒂姆说:“我们首先解决了急性髓细胞白血病,因为它是一种异质复杂的疾病,65岁以上急性骨髓性白血病患者的一年存活率大约低于20%,相比之下,乳腺癌的一年存活率超过90% 。老年AML患者的成活率非常低的原因之一可能是由于一般来说,它们不能耐受高剂量的常规药物,如阿糖胞苷和柔红霉素,而且老年人通常不适用同种异体造血细胞移植的候选人,来延长寿命几年。
 
“急性骨髓性白血病也没有像其他癌症一样大的患者人群,所以也许消耗资源来寻找抗逆转录酶治疗的动机并不是那么大。”
 
Sintim说,约30%的急性髓细胞白血病患者在称为FLT 3的蛋白激酶中发生突变,这被称为驱动急性骨髓性白血病的驱动突变。
 
他说:“目前有针对FLT3的抑制剂,但是临床试验表明,经过几个月的治疗后,二次突变将形成使得抑制剂无效,因此癌症将恢复。目前没有单一的FLT3激酶抑制剂提供彻底治愈急性髓细胞白血病。我们开发了一个平台来创建不仅靶向FLT3的新型分子,而且还针对增强FLT3信号传导或可能出现并恢复癌症的其他信号通路。我们相信我们的化合物可以处理这些二次突变,可能完全治愈。”
 
Sintim补充说,该技术可以适应于治疗其他没有有效治疗剂的癌症。
 
他说:“我们的第一个目标是开发技术,使我们能够快速开发可以完全抑制蛋白激酶的新化学物质,我们的平台可用于快速探索化学空间,可以靶向需要抑制剂的几乎任何蛋白激酶化合物不仅适用于急性髓细胞白血病。我们相信我们的平台也可以应用于某些类型的肺癌,乳腺癌和甲状腺癌,由蛋白激酶驱动并遭受二次突变的不同癌症。”
 
普渡研究基金会技术商业化办公室已将该技术授予专利。 Sintim正在寻求有兴趣研究或进一步开发化合物的合作伙伴。
 
他说:“我们已经做了一些初步的动物临床研究,显示我们的化合物在小鼠急性髓细胞白血病模型中有效地工作,我们有信心经过进一步的发展,我们将能够开发出一种完整的抗急性髓细胞白血病的治疗药物。”

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    2017-11-04 quxin068
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    2017-05-01 jyzxjiangqin

    新型药物杀灭癌细胞无毒吏有效。

    0

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    2017-04-28 yxch36
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    2017-04-27 明天会更好!

    学习过了,增长了知识。

    0

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    2017-04-27 flysky120

    希望能彻底治疗癌症

    0

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