Residential College | false |
Status | 已發表Published |
Development of a sensitive luminescent probe to uncover new BRD4 inhibitors in living cells | |
Song, Ying Qi1; Wu, Ke Jia1; Zhang, Zhiming2; Liu, Tzu-Ming2; Ko, Chung Nga3; Zhu, Wei Guo4; Ma, Dik Lung3; Wang, Wanhe3,5; Leung, Chung Hang1,6 | |
2023-03-11 | |
Source Publication | Chemical Engineering Journal |
ISSN | 1385-8947 |
Volume | 463Pages:142356 |
Abstract | Bromodomain-containing protein 4 (BRD4) is a reader of acetylated histones that regulates the invasion, metastasis and proliferation of cancer. Inhibition of BRD4 activity is an emerging strategy for anticancer. In this study, an iridium based-luminescent probe for screening BRD4 inhibitors in cellulo was developed. The K293 probe was designed by linking a BRD4 nuclear translocation inhibitor as a “binding unit” to an iridium complex as a luminescent “signal unit”. K293 selectively binds to BRD4 in living cancer cells. Candidate compounds compete with K293 for BRD4, resulting in a decrease in luminescence signal. The long luminescence lifetime of K293 allows its luminescence signal to be distinguished from interfering fluorescence using time-resolved techniques in order to improve sensitivity. Hence, even potential BRD4 inhibitors that are undetectable by conventional fluorescence methods can be identified. As a proof-of-concept, Azelastine, an FDA-approved histamine 1 (H) antagonist was identified to be a potential BRD4 inhibitor using the K293 probe. Azelastine binds to BRD4 protein in the cytoplasm to prevent its translocation into the nucleus, and suppresses cancer cell growth and migration. The results demonstrated that the probe could be useful for the future drug repurposing. |
Keyword | Azelastine Brd4 Drug Screening Inhibitor Luminescent Probe |
DOI | 10.1016/j.cej.2023.142356 |
URL | View the original |
Indexed By | SCIE |
Language | 英語English |
WOS Research Area | Engineering |
WOS Subject | Engineering, Environmental ; Engineering, Chemical |
WOS ID | WOS:000955345800001 |
Publisher | ELSEVIER SCIENCE SA, PO BOX 564, 1001 LAUSANNE, SWITZERLAND |
Scopus ID | 2-s2.0-85150225153 |
Fulltext Access | |
Citation statistics | |
Document Type | Journal article |
Collection | Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau Faculty of Health Sciences Institute of Chinese Medical Sciences THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU) Institute of Translational Medicine DEPARTMENT OF BIOMEDICAL SCIENCES |
Co-First Author | Song, Ying Qi |
Corresponding Author | Ma, Dik Lung; Wang, Wanhe; Leung, Chung Hang |
Affiliation | 1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China 2.Institute of Translational Medicine, Faculty of Health Sciences & Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau, China 3.Department of Chemistry, Hong Kong Baptist University, Hong Kong 4.Department of Biochemistry and Molecular Biology, Shenzhen University School of Medicine, Shenzhen, China 5.Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 127 West Youyi Road, Shaanxi, 710072, China 6.Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Macao, China |
First Author Affilication | Institute of Chinese Medical Sciences |
Corresponding Author Affilication | Institute of Chinese Medical Sciences; Faculty of Health Sciences |
Recommended Citation GB/T 7714 | Song, Ying Qi,Wu, Ke Jia,Zhang, Zhiming,et al. Development of a sensitive luminescent probe to uncover new BRD4 inhibitors in living cells[J]. Chemical Engineering Journal, 2023, 463, 142356. |
APA | Song, Ying Qi., Wu, Ke Jia., Zhang, Zhiming., Liu, Tzu-Ming., Ko, Chung Nga., Zhu, Wei Guo., Ma, Dik Lung., Wang, Wanhe., & Leung, Chung Hang (2023). Development of a sensitive luminescent probe to uncover new BRD4 inhibitors in living cells. Chemical Engineering Journal, 463, 142356. |
MLA | Song, Ying Qi,et al."Development of a sensitive luminescent probe to uncover new BRD4 inhibitors in living cells".Chemical Engineering Journal 463(2023):142356. |
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