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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 PublicationChemical Engineering Journal
ISSN1385-8947
Volume463Pages: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.

KeywordAzelastine Brd4 Drug Screening Inhibitor Luminescent Probe
DOI10.1016/j.cej.2023.142356
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaEngineering
WOS SubjectEngineering, Environmental ; Engineering, Chemical
WOS IDWOS:000955345800001
PublisherELSEVIER SCIENCE SA, PO BOX 564, 1001 LAUSANNE, SWITZERLAND
Scopus ID2-s2.0-85150225153
Fulltext Access
Citation statistics
Document TypeJournal article
CollectionMinistry 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 AuthorSong, Ying Qi
Corresponding AuthorMa, Dik Lung; Wang, Wanhe; Leung, Chung Hang
Affiliation1.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 AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute 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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