Novel brd4 inhibitors with a unique scaffold exhibit antitumor effectsopen access
- Authors
- Kim, Young Hun; Kim, Minsung; Kim, Ji Eun; Yoo, Miyoun; Lee, Heung Kyoung; Lee, Chong Ock; Yoo, Minjin; Jung, Kwan-Young; Kim, Yeongrin; Choi, Sang Un; Park, Chi Hoon
- Issue Date
- Jun-2021
- Publisher
- SPANDIDOS PUBL LTD
- Keywords
- bromodomain inhibitor; novel scaffold; anticancer agent; mid-throughput screening; brd4
- Citation
- ONCOLOGY LETTERS, v.21, no.6
- Indexed
- SCIE
SCOPUS
- Journal Title
- ONCOLOGY LETTERS
- Volume
- 21
- Number
- 6
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/924
- DOI
- 10.3892/ol.2021.12734
- ISSN
- 1792-1074
1792-1082
- Abstract
- Since bromodomain containing 4 (brd4) has been considered as a prominent cancer target, numerous attempts have been made to develop potent brd4 bromodomain inhibitors. The present study provided a novel chemical scaffold which inhibited brd4 activity. Mid-throughput screening against brd4 bromodomain was performed using alpha-screen and homogeneous time-resolved fluorescence assays. Furthermore, cell cytotoxicity and xenograft assays were performed to examine if the compound was effective both in vitro and in vivo. As a result, it was revealed that compounds having naphthalene-1,4-dione scaffold inhibited the binding of bromodomain to acetylated histone. The compounds with naphthalene-1,4-dione had cytotoxic effects against the Ty82 cell line, a NUT midline carcinoma cell line, whose proliferation is dependent on brd4 activity. A10, one of the compounds with naphthalene-1,4-dione scaffold, also exhibited tumor growth inhibition effects in the xenograft assay. In addition, the compounds exhibited cytotoxic effects against gastric cancer cell lines which were resistant to I-BET-762, a BET bromodomain inhibitor. In conclusion, the novel scaffold to suppress brd4 activity was effective against cancer cells both in vitro and in vivo.
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Collections - Pharmacy > Department of Pharmacy > 1. Journal Articles
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