Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells. Sci Rep. 2016; 6:24218. https://doi. org/10.1038/srep24218.Lan, H.; Tang, Z.; Jin, H.; Sun, Y. Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells. Sci. ...
TAS4464是Taiho制药开发的另一个选择性NAE抑制剂,是第二个进入临床的NAE小分子抑制剂,IC50为0.955 nM,活性高于MLN4924,此外,TAS4464对脱靶靶点碳酸酐酶II抑制活性低(IC50= 0.73μM),目前处于治疗多发性骨髓瘤和非霍奇金淋巴瘤的临床一/二期和治疗血液恶性肿瘤和实体瘤的临床一期。化合物1是利用骨架跃迁策略从MLN4924...
本研究发现重要抑癌蛋白PTEN为Neddylation修饰新底物，Neddylation逆转PTEN蛋白的抑癌功能并促进乳腺癌的发生发展，该工作揭示了重要抑癌蛋白PTEN的全新翻译后修饰，丰富了临床上部分肿瘤中PTEN失活的可能机制，拓展了人们对Neddylation功能的认知，为MLN4924应用于临床乳腺癌治疗提供分类治疗和精准治疗的参考依据。 他们发现：...
Li等[40]的研究显示,MLN4924 通过诱导CRL的底物核因子κB抑制蛋白α(Inhibitor of kappa B α,IκBα)的大量累积抑制核因子κB的活性,从而降低脂多糖诱导的巨噬细胞中肿瘤坏死因子α和白介素6的产生,并进一步通过诱导巨噬细胞系RAW264.7...
Neddylation修饰通路的小分子抑制剂 MLN4924可以诱导肺癌细胞发生细胞周期阻滞、细胞凋亡和衰老,发挥抗肺癌作用。此外,通过靶向 Neddylation修饰通路关键酶及其底物 Cullin家族蛋白也可以抑制肺癌发生发展。 【关键词】 肺肿瘤;分子靶向治疗;Neddylation 基金项目:国家自然科学基金(81902380);国家高技术研究发展计... ...
MLN4924 is a recently discovered small molecule inhibitor of NEDD8-Activating Enzyme (NAE). Because cullin RING ligase (CRL), the largest family of E3 ubiquitin ligase, requires cullin neddylation for its activity, MLN4924, therefore, acts as an indirect inhibitor of CRL by blocking cullin neddyla...
In addition, MLN4924 could enhance the induction of intracellular and mitochondrial reactive oxygen species (ROS) under hypoxia. These results indicate that the neddylation inhibitor MLN4924 potentiates hypoxia-induced apoptosis of mouse type B spermatogonia GC-2 cells, and neddylation may play an ...
Brownell JE, Sintchak MD, Gavin JM, Liao H, Bruzzese FJ, Bump NJet al. Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimeticIn Situ.Mol Cell2010;37: 102–111. ...
Neddylation修饰通路的小分子抑制剂MLN4924可以诱导肺癌细胞发生细胞周期阻滞、细胞凋亡和衰老,发挥抗肺癌作用。此外,通过靶向Neddylation修饰通路关键酶及其底物Cullin家族蛋白也可以抑制肺癌发生发展。 关键词: 肺肿瘤;分子靶向治疗;Neddylation ABSTRACT Neddylation is overactivated in lung cancer, which promotes the ...
MLN4924 is a recently discovered small molecule inhibitor of NEDD8-Activating Enzyme (NAE). Because cullin RING ligase (CRL), the largest family of E3 ubiquitin ligase, requires cullin neddylation for its activity, MLN4924, therefore, acts as an indirect inhibitor of CRL by blocking cullin neddyla...