1923749-80-7Relevant academic research and scientific papers
Optimization of 5-arylidene barbiturates as potent, selective, reversible LSD1 inhibitors for the treatment of acute promyelocytic leukemia
Xu, Siyuan,Zhou, Chen,Liu, Rongfeng,Zhu, Qihua,Xu, Yungen,Lan, Fei,Zha, Xiaoming
, p. 4871 - 4880 (2018)
Histone lysine specific demethylase 1 (LSD1) is overexpressed in diverse hematologic disorders and recognized as a promising target for blood medicines. In this study, molecular docking-based virtual screening united with bioevaluation was utilized to identify novel skeleton of 5-arylidene barbiturate as small-molecule inhibitors of LSD1. Among the synthesized derivatives, 12a exhibited reversible and potent inhibition (IC50 = 0.41 μM) and high selectivity over the MAO-A and MAO-B. Notably, 12a strongly induced differentiation effect on acute promyelocytic leukemia NB4 cell line and distinctly escalated the methylation level on histone 3 lysine 4 (H3K4). Our findings indicate that 5-arylidene barbiturate may represent a new skeleton of LSD1 inhibitors and 12a deserve as a promising agent for the further research.
Barbiturate compound, preparing method and application thereof
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Paragraph 0047; 0048; 0049; 0080; 0081; 0082, (2016/10/09)
The invention belongs to the field of medicinal chemistry, and discloses a barbiturate compound, a preparing method and application thereof. Specifically, the invention relates to the compound as shown in formula I, and a medicinal usage thereof as a selective LSD1 reversible inhibitor, particular to the application in preparing of antitumor medicine. A test shows that the compound in formula I can efficiently reversibly inhibit LSD1 activity, and has a weak inhibition action for homologous proteins MAO-A and MAO-B, can intensively induce differentiation of leukemia cell NB4 and obviously enhance the methylation level of primers H3K4me1 and H3K4me2 of the LSD1.
