@article{b9438f811d7a4ffab495b7c770dd8479,
title = "A robust photoluminescence screening assay identifies uracil-DNA glycosylase inhibitors against prostate cancer",
abstract = "Many cancers have developed resistance to 5-FU, due to removal by the enzyme uracil-DNA glycosylase (UDG), a type of base excision repair enzyme (BER) that can excise uracil and 5-fluorouracil (5-FU) from DNA. However, the development of UDG inhibitor screening methods, especially for the rapid and efficient screening of natural product/natural product-like compounds, is still limited so far. We developed herein a robust time-resolved photoluminescence method for screening UDG inhibitors, which could significantly improve sensitivity over the screening method based on the conventional steady-state spectroscopy, reducing the substantial fluorescence background interference. As a proof-of-concept, two potential UDG inhibitors were identified from a database of natural products and approved drugs. Co-treatment of these two compounds with 5-FU showed synergistic cytotoxicity, providing the basis for treating drug-resistant cancers. Overall, this method provides an avenue for the rapid screening of small molecule regulators of other BER enzyme activities that can avoid false negatives arising from the background fluorescence.",
author = "Guodong Li and Henry, {Stuart Adam} and Hao Liu and Kang, {Tian Shu} and Nao, {Sang Cuo} and Yichao Zhao and Chun Wu and Jianwen Jin and Zhang, {Jia Tong} and Leung, {Chung Hang} and {Wai Hong Chan}, Philip and Ma, {Edmond Dik Lung}",
note = "Funding Information: We would like to thank Feng Chen (University of Macau) for technical assistance. This work was supported by Hong Kong Baptist University (FRG2/17-18/003), the Health and Medical Research Fund (HMRF/14150561), the National Natural Science Foundation of China (21575121 and 21775131), the Guangdong Province Natural Science Foundation (2015A030313816), the Hong Kong Baptist University Century Club Sponsorship Scheme 2018, the Interdisciplinary Research Matching Scheme (RC-IRMS/16-17/03), Interdisciplinary Research Clusters Matching Scheme (RC-IRCs/17-18/03), Collaborative Research Fund (C5026-16G), SKLEBA and HKBU Strategic Development Fund (SKLP_1718_P04), Funded by The Science and Technology Development Fund, Macau SAR (File no. 077/2016/A2), the University of Macau (MYRG2018-00187-ICMS and MYRG2019-00002-ICMS), and a Discovery Project Grant (DP160101682, Australia) from the Australian Research Council.",
year = "2020",
month = feb,
day = "21",
doi = "10.1039/c9sc05623h",
language = "English",
volume = "11",
pages = "1750--1760",
journal = "Chemical Science",
issn = "2041-6520",
publisher = "Royal Society of Chemistry",
number = "7",
}