对向LOXL2的共价抑制剂查:通过虚拟查和实验验证进行研究
Lirui Lin1,2,3,4, Kai Lin2, Lichun Chen2
1Department of Bioinformatics, Shantou University Medical College, Shantou, 515041, PR China.
Recent patents on anti-cancer drug discovery
|January 6, 2025
概括
研究人员选了共价抑制剂的酸氧化酶样2 (LOXL2),一种促进瘤转移的酶. 一种有前途的化合物F50972176被确定,在伤口愈合试验中有效抑制了癌细胞迁移.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 类似酸氧化酶2 (LOXL2) 是一种金属酶,涉及促进瘤转移和入侵.
- 二硫化物键对LOXL2生物活性至关重要,可以被小分子准.
- 协同抑制剂提供了一种策略,通过阻断二硫化物键形成来调节LOXL2功能.
研究的目的:
- 选和识别LOXL2.2的新型共价抑制剂.
- 为了研究向LOXL2二硫化物键在癌症治疗中的潜力.
主要方法:
- 使用施罗丁格的CovDock对共价分子库进行虚拟选.
- 使用LigPrep.rep进行结构优化和符合性生成.
- 通过伤口愈合试验进行实验验证.
主要成果:
- 在7,908名候选人中,发现了8种潜在的共价抑制剂.
- 所有选择的化合物都通过了ADMET评估.
- 化合物F50972176显示显著抑制癌细胞迁移.
结论:
- 虚拟查与实验验证相结合,可有效识别LOXL2共价抑制剂.
- 化合物F50972176显示出抑制食道状细胞癌细胞迁移的潜力.
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