Fragment-based design, synthesis and biological evaluation of theophylline derivatives as ATAD2 inhibitors in BT-549 cells
ATPase family AAA domain-containing protein 2 (ATAD2) has been emerging as a hot anti-cancer drugable target due to its oncogenic epigenetic modification closely associated with cancer cells proliferation, apoptosis, migration and drug resistance. In this study, we design a series of theophylline de...
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| Format: | Book |
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Taylor & Francis Group,
2023-12-01T00:00:00Z.
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|---|---|---|---|
| 001 | doaj_0d14eec2e9ba4abb98fa3bc4dd4a514d | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Dahong Yao |e author |
| 700 | 1 | 0 | |a Jieshu You |e author |
| 700 | 1 | 0 | |a Xuetao Yang |e author |
| 700 | 1 | 0 | |a Jin Zhang |e author |
| 700 | 1 | 0 | |a Xiaojun Yao |e author |
| 245 | 0 | 0 | |a Fragment-based design, synthesis and biological evaluation of theophylline derivatives as ATAD2 inhibitors in BT-549 cells |
| 260 | |b Taylor & Francis Group, |c 2023-12-01T00:00:00Z. | ||
| 500 | |a 10.1080/14756366.2023.2242601 | ||
| 500 | |a 1475-6374 | ||
| 500 | |a 1475-6366 | ||
| 520 | |a ATPase family AAA domain-containing protein 2 (ATAD2) has been emerging as a hot anti-cancer drugable target due to its oncogenic epigenetic modification closely associated with cancer cells proliferation, apoptosis, migration and drug resistance. In this study, we design a series of theophylline derivatives as novel ATAD2 inhibitors through fragment-based screening and scaffold growth strategy. A novel potent ATAD2 inhibitor (compound 19f) is discovered with an IC50 value of 0.27 μM against ATAD2, which adopts a combination of classic and atypical binding mode. Additionally, compound 19f could impede ATAD2 activity and c-Myc activation, induced significant apoptosis, and illustrated an anti-migration effect in BT-549 cells. Collectively, these results provide new enlightenment for the development of novel potent ATAD2 inhibitors for triple-negative breast cancer (TNBC) treatment. | ||
| 546 | |a EN | ||
| 690 | |a ATAD2 | ||
| 690 | |a fragment-based | ||
| 690 | |a TNBC | ||
| 690 | |a apoptosis | ||
| 690 | |a migration | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 38, Iss 1 (2023) | |
| 787 | 0 | |n https://www.tandfonline.com/doi/10.1080/14756366.2023.2242601 | |
| 787 | 0 | |n https://doaj.org/toc/1475-6366 | |
| 787 | 0 | |n https://doaj.org/toc/1475-6374 | |
| 856 | 4 | 1 | |u https://doaj.org/article/0d14eec2e9ba4abb98fa3bc4dd4a514d |z Connect to this object online. |