Discovery of orally active chalcones as histone lysine specific demethylase 1 inhibitors for the treatment of leukaemia
Histone lysine specific demethylase 1 (LSD1) has emerged as an attractive molecule target for the discovery of potently anticancer drugs to treat leukaemia. In this study, a series of novel chalcone derivatives were designed, synthesised and evaluated for their inhibitory activities against LSD1 in ...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Book |
| Published: |
Taylor & Francis Group,
2021-01-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
MARC
| LEADER | 00000 am a22000003u 4500 | ||
|---|---|---|---|
| 001 | doaj_a4879addcf6a4704b05a41cb151028a6 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Yang Li |e author |
| 700 | 1 | 0 | |a Ying Sun |e author |
| 700 | 1 | 0 | |a Yang Zhou |e author |
| 700 | 1 | 0 | |a Xinyang Li |e author |
| 700 | 1 | 0 | |a Huan Zhang |e author |
| 700 | 1 | 0 | |a Guojun Zhang |e author |
| 245 | 0 | 0 | |a Discovery of orally active chalcones as histone lysine specific demethylase 1 inhibitors for the treatment of leukaemia |
| 260 | |b Taylor & Francis Group, |c 2021-01-01T00:00:00Z. | ||
| 500 | |a 1475-6366 | ||
| 500 | |a 1475-6374 | ||
| 500 | |a 10.1080/14756366.2020.1852556 | ||
| 520 | |a Histone lysine specific demethylase 1 (LSD1) has emerged as an attractive molecule target for the discovery of potently anticancer drugs to treat leukaemia. In this study, a series of novel chalcone derivatives were designed, synthesised and evaluated for their inhibitory activities against LSD1 in vitro. Among all these compounds, D6 displayed the best LSD1 inhibitory activity with an IC50 value of 0.14 μM. In the cellular level, compound D6 can induce the accumulation of H3K9me1/2 and inhibit cell proliferation by inactivating LSD1. It exhibited the potent antiproliferative activity with IC50 values of 1.10 μM, 3.64 μM, 3.85 μM, 1.87 μM, 0.87 μM and 2.73 μM against HAL-01, KE-37, P30-OHK, SUP-B15, MOLT-4 and LC4-1 cells, respectively. Importantly, compound D6 significantly suppressed MOLT-4 xenograft tumour growth in vivo, indicating its great potential as an orally bioavailable candidate for leukaemia therapy. | ||
| 546 | |a EN | ||
| 690 | |a histone lysine specific demethylase 1 | ||
| 690 | |a chalcone | ||
| 690 | |a h3k9me1/2 | ||
| 690 | |a leukaemia | ||
| 690 | |a molt-4 xenograft | ||
| 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 36, Iss 1, Pp 207-217 (2021) | |
| 787 | 0 | |n http://dx.doi.org/10.1080/14756366.2020.1852556 | |
| 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/a4879addcf6a4704b05a41cb151028a6 |z Connect to this object online. |