基于结构的虚拟查和MARK4抑制剂的实验验证,用于向癌症治疗
Sarfraz Ahmed1,2, Mohd Shakir1,3, Haider Thaer Abdulhameed Almuqdadi1,4
1Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
Journal of biomolecular structure & dynamics
|January 27, 2026
概括
使用虚拟查识别了微管亲和调节激酶4 (MARK4) 抑制剂. JMI-1094表现出强烈的结合,并抑制MARK4活性,降低癌细胞活力和迁移.
科学领域:
- 生物化学和分子生物学
- 药理学 药理学是指药理学的学科.
- 计算化学计算化学
背景情况:
- 微管类亲和调节酶4 (MARK4) 是神经退行性疾病和癌症的治疗点.
- 鉴定MARK4的小分子抑制剂对于治疗开发至关重要.
研究的目的:
- 确定针对MARK4.4的新型小分子抑制剂.
- 评估已识别的抑制剂的结合亲和力,稳定性和疗效.
主要方法:
- 使用施罗丁格Maestro套件进行虚拟高吞吐量选.
- 分子对接,Prime/MM-GBSA和分子动力学 (MD) 模拟.
- 基于细胞的陶酸化试验和癌细胞系活力研究 (MCF-7,A549).
主要成果:
- JMI-1094被确定为一个有前途的MARK4抑制剂,其对接得分为-8.486 kcal/mol.
- MD模拟证实了JMI-1094与MARK4的稳定结合,关键相互作用仍然存在.
- JMI-1094显著抑制了MARK4活性,降低了活力 (IC50:MCF-7中的4.14μM,A549中的6.22μM),并减少了癌细胞的迁移.
结论:
- JMI-1094是一种强大的MARK4抑制剂,具有已证明的抗癌作用.
- JMI-1094对MARK4介导的癌症具有潜在的治疗意义.
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