A novel pyrrole-imidazole polyamide targets Aurora kinase A and suppresses tumor growth in vivo

Li，Meiqing1,2; Lu，Danyi1,3; Cheng，Yulian1,4; Wu，Chunlei1; Zhang，Jianchao5; Shi，Wenli6,7; Ding，Zhihao1; Li，Yanyan1,2; Cheng，Binghua1,2; Lin，Xian1; Shao，Ximing1; Li，Hongchang1; Fang，Lijing1; Liu，Ke1; Su，Wu1

2021-09-24

10.1016/j.bbrc.2021.07.077

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   影响因子和分区

0006-291X

1090-2104

Aurora kinase A (Aurora A) plays a critical role in regulating cell mitotic progression and has been considered as a promising drug target for cancer therapy. To develop a novel molecule targeting Aurora A with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide (PIP) Hoechst conjugate, PIP-Ht, targeting to a cell-cycle regulated DNA sequence locating at the promoter of human Aurora A gene (AURKA). PIP-Ht potently suppressed AURKA promoter activities, mRNA expression and protein level, induced tumor cell cycle delay and inhibited tumor cell proliferation in vitro. Furthermore, subcutaneous injection of PIP-Ht into mice bearing human cancer xenografts induced significant tumor growth suppression and cell apoptosis. Collectively, PIP-Ht exhibits the potential as an effective therapeutic candidate for the tumor treatment.

Aurora A inhibitor Pyrrole-imidazole polyamide Tumor cell-cycle

SCI

英语

其他

WOS:000678532600006

BIOLOGY & BIOCHEMISTRY

2-s2.0-85111211348

Scopus

1.Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,518055,China
2.University of Chinese Academy of Sciences,Beijing,100049,China
3.Institute of Molecular Rhythm and Metabolism,School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou,510006,China
4.Nano Science and Technology Institute,University of Science and Technology of China,Suzhou,215123,China
5.Department of Biochemistry,School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
6.School of Life and Pharmaceutical Sciences,Hainan University,Haikou,570228,China
7.Hainan Key Laboratory for Sustainable Utilization of Tropical Bioresources,College of Tropical Crops,Hainan University,Haikou,570228,China

Li，Meiqing,Lu，Danyi,Cheng，Yulian,et al. A novel pyrrole-imidazole polyamide targets Aurora kinase A and suppresses tumor growth in vivo[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2021,571:167-173.

Li，Meiqing.,Lu，Danyi.,Cheng，Yulian.,Wu，Chunlei.,Zhang，Jianchao.,...&Su，Wu.(2021).A novel pyrrole-imidazole polyamide targets Aurora kinase A and suppresses tumor growth in vivo.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,571,167-173.

Li，Meiqing,et al."A novel pyrrole-imidazole polyamide targets Aurora kinase A and suppresses tumor growth in vivo".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 571(2021):167-173.