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含的PI3Kδ抑制剂的设计,合成和生物活性评估

Li Gao¹, Hongyan Chuai¹, Mengyan Ma¹

¹School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.

Bioorganic chemistry

|September 6, 2023

概括

含有的化合物,如Se15,是新型,强效和选择性的酸酸3-激酶三角酶 (PI3Kδ) 抑制剂. 这一发现为治疗白血病,淋巴瘤和自身免疫性疾病提供了新的途径.

科学领域:

药用化学医学化学
药物发现药物发现药物发现
药理学药理学是指药理学的学科.

背景情况:

酸3-酶三角酶 (PI3Kδ) 抑制剂对于治疗各种癌症和自身免疫性疾病至关重要.
现有的PI3Kδ抑制剂为开发新治疗剂提供了基础.

研究的目的:

设计和合成含的新型PI3Kδ抑制剂.
评估这些新化合物对PI3Kδ的抑制活性和选择性.
探索在PI3Kδ抑制剂开发中的潜力.

主要方法:

基于金纳和pyrido[3,2-d]pyrimidine支架的含化合物的设计和合成.
在体外酶分析以确定PI3Kδ抑制和选择性.
使用SU-DHL-6细胞进行基于细胞的抗增殖试验.
分子对接研究以阐明与PI3Kδ的结合相互作用.

主要成果:

化合物Se15显示出对PI3Kδ的亚纳米抑制,具有高的δ选择性.
Se15对SU-DHL-6细胞表现出强烈的抗增殖作用 (IC50 = 0.16μM).
分子对接揭示了Se15与PI3Kδ活性部位之间的有利相互作用,包括结和堆叠.

结论:

含的化合物Se15,具有pyrido[3,2-d]pyrimidine支架,是一种强效和选择性的PI3Kδ抑制剂.
将纳入抑制剂结构为开发新型PI3Kδ向治疗提供了一个有希望的策略.
这项研究为对抗各种疾病的下一代PI3Kδ抑制剂的设计提供了新的方向.

关键词:

在白血病中,白血病.的PI3Kδ抑制剂.皮里多[3,2-d] 皮里米丁.这是一种Se-methylselenocysteine.是一种.

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