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Discovery of novel ATAD2 bromodomain inhibitors that trigger apoptosis and autophagy in breast cells by structure-based virtual screening.

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资源类型：
Pubmed体系：
作者：
Dahong Yao[a,b] ; Jin Zhang[c] ; Jinhui Wang[d] ; Dabo Pan[e,*a] ; Zhendan He[a,b,*b] ;
机构： [a]Guangdong Key Laboratory for Genome Stability & Human Disease Prevention, School of Pharmaceutical Sciences, Shenzhen University,Shenzhen, China [b]Shenzhen Key Laboratory of Novel Natural Health Care Products, Innovation Platform for Natural small molecule Drugs,Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Shenzhen University Health Science Center, Shenzhen, China [c]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy,Chengdu, China [d]Shenzhen Honghui Bio-Pharmaceutical Co. Ltd., Shenzhen, China [e]Institute of Traditional Chinese Medicine & NaturalProducts, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, JinanUniversity, Guangzhou, P. R. China
出处：
DOI： 10.1080/14756366.2020.1740924
ISSN：

关键词： ATAD2 breast cancer Virtual Screening apoptosis autophagy

摘要：
ATAD2 has been reported to play an important role in the processes of numerous cancers and validated to be a potential therapeutic target. This work is to discover potent ATAD2 inhibitors and elucidate the underlying mechanisms in breast cancer. A novel ATAD2 bromodomain inhibitor (AM879) was discovered by combining structure-based virtual screening with biochemical analyses. AM879 presents potent inhibitory activity towards ATAD2 bromodomain (IC50 = 3565 nM), presenting no inhibitory activity against BRD2-4. Moreover, AM879 inhibited MDA-MB-231 cells proliferation with IC50 value of 2.43 µM, suppressed the expression of c-Myc, and induced significant apoptosis. Additionally, AM978 could induce autophagy via PI3K-AKT-mTOR signalling in MDA-MB-231 cells. This study demonstrates the development of potent ATAD2 inhibitors with novel scaffolds for breast cancer therapy.

基金：
This work was received the supported of National Natural Science Foundation of China [81803365, 81803347, 31670360 and 81973293], the National Key R & D Programme of China [2017YFA0503900, 2018ZX09735-005], and Post-Doctor Research Project [2018M643510, 2019M650213], the Natural Science Foundation of Guangdong Province 2018A030313707. The authors have no other relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类 | 2 区 医学
小类 | 2 区 生化与分子生物学 2 区 药物化学
最新[2023]版：
大类 | 2 区 医学
小类 | 2 区 生化与分子生物学 2 区 药物化学
第一作者：
第一作者机构： [a]Guangdong Key Laboratory for Genome Stability & Human Disease Prevention, School of Pharmaceutical Sciences, Shenzhen University,Shenzhen, China [b]Shenzhen Key Laboratory of Novel Natural Health Care Products, Innovation Platform for Natural small molecule Drugs,Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Shenzhen University Health Science Center, Shenzhen, China
通讯作者：
通讯机构： [a]Guangdong Key Laboratory for Genome Stability & Human Disease Prevention, School of Pharmaceutical Sciences, Shenzhen University,Shenzhen, China [b]Shenzhen Key Laboratory of Novel Natural Health Care Products, Innovation Platform for Natural small molecule Drugs,Engineering Laboratory of Shenzhen Natural small molecule Innovative Drugs, Shenzhen University Health Science Center, Shenzhen, China [e]Institute of Traditional Chinese Medicine & NaturalProducts, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, JinanUniversity, Guangzhou, P. R. China [*a]Institute of Traditional Chinese Medicine & Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, P. R. China [*b]Guangdong Key Laboratory for Genome Stability & Human Disease Prevention, School of Pharmaceutical Sciences, Shenzhen University, Shenzhen, 518060, China
推荐引用方式(GB/T 7714)：
Dahong Yao,Jin Zhang,Jinhui Wang,et al.Discovery of novel ATAD2 bromodomain inhibitors that trigger apoptosis and autophagy in breast cells by structure-based virtual screening.[J].Journal of enzyme inhibition and medicinal chemistry.2020,35(1):713-725.doi:10.1080/14756366.2020.1740924.
APA：
Dahong Yao,Jin Zhang,Jinhui Wang,Dabo Pan&Zhendan He.(2020).Discovery of novel ATAD2 bromodomain inhibitors that trigger apoptosis and autophagy in breast cells by structure-based virtual screening..Journal of enzyme inhibition and medicinal chemistry,35,(1)
MLA：
Dahong Yao,et al."Discovery of novel ATAD2 bromodomain inhibitors that trigger apoptosis and autophagy in breast cells by structure-based virtual screening.".Journal of enzyme inhibition and medicinal chemistry 35..1(2020):713-725

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