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通过基于结构的虚拟查,生物评估和MD模拟来发现小型ERK5抑制剂

Noor Atatreh^1,2, Radwa E Mahgoub^1,2, Rose Ghemrawi^1,2

¹College of Pharmacy, Al Ain University, Abu Dhabi 64141, United Arab Emirates.

Molecules (Basel, Switzerland)

|November 13, 2025

概括

研究人员通过虚拟查和细胞检测确定了新型ERK5抑制剂. 化合物STK300222和GR04显示出显著的抗增殖和抗迁移作用,显示出癌症治疗开发的潜力.

科学领域:

生物化学和分子生物学
药用化学医学化学
计算机化药物发现技术

背景情况:

细胞外信号调节激酶5 (ERK5) 是一种涉及癌症进展的MAP激酶.
ERK5调节关键的细胞过程,包括增殖,生存和迁移.
向ERK5是各种癌症的潜在治疗策略.

研究的目的:

通过基于结构的虚拟查来识别ERK5的新型抑制剂.
评估已识别的化合物的反扩散和反迁移活动.
评估化合物与ERK5.5的结合稳定性和亲和力.

主要方法:

基于结构的虚拟选160万个化合物使用施罗丁格Maestro.
通过MTT测定在A549和H292肺癌细胞系中评估的抗增殖活性.
分子动力学模拟和MM-GB/SA评分以评估结合稳定性和亲和力.

主要成果:

40个候选化合物被确定具有优越的对接分数.
化合物STK038175,STK300222和GR04表现出显著的抗增殖活性 (IC50:10-25μM).
STK300222降低了ERK5酸化和细胞迁移;MD模拟证实了STK300222和GR04.04的稳定结合和强相互作用.

结论:

STK300222和GR04是有前途的ERK5抑制剂,具有显著的抗增殖和抗迁移作用.
这些化合物表现出与ERK5的稳定结合,与共结晶的配体相美.
对于STK300222和GR04的进一步优化和体内验证是癌症治疗开发的必要条件.

关键词:

在ERK5中,ERK5是ERK5.抗癌剂是一种抗癌剂.发现药物的发现.抑制剂抑制剂的使用肺癌是一种肺癌.虚拟选虚拟选虚拟选

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