13961-05-2Relevant articles and documents
Synthesis and evaluation of 1H-pyrrole-2,5-dione derivatives as cholesterol absorption inhibitors for suppressing the formation of foam cells and inflammatory response
Yuan, Xinrui,Xia, Yineng,Lu, Peng,Zhu, Lijuan,Zhong, Yuejiao,Wang, Yubin
, p. 1435 - 1447 (2018)
Excess lipid accumulation in the arterial intima and formation of macrophage-derived foam cells in the plaque could cause atherosclerotic lesion. Cholesterol absorption inhibitors could suppress the lipid accumulation of human macrophage, inflammatory res
DMSO-Enabled Selective Radical O?H Activation of 1,3(4)-Diols
Han, Bing,Jiao, Ning,Jin, Rui,Liu, Guoquan,Liu, Jianzhong,Zhang, Ziyao,Zhu, Yuchao
supporting information, p. 19851 - 19856 (2020/09/04)
Control of selectivity is one of the central topics in organic chemistry. Although unprecedented alkoxyl-radical-induced transformations have drawn a lot of attention, compared to selective C?H activation, selective radical O?H activation remains less explored. Herein, we report a novel selective radical O?H activation strategy of diols by combining spatial effects with proton-coupled electron transfer (PCET). It was found that DMSO is an essential reagent that enables the regioselective transformation of diols. Mechanistic studies indicated the existence of the alkoxyl radical and the selective interaction between DMSO and hydroxyl groups. Moreover, the distal C?C cleavage was realized by this selective alkoxyl-radical-initiation protocol.
Identification of novel small-molecule inhibitors targeting menin-MLL interaction, repurposing the antidiarrheal loperamide
Yue, Liyan,Du, Juanjuan,Ye, Fei,Chen, Zhifeng,Li, Lianchun,Lian, Fulin,Zhang, Bidong,Zhang, Yuanyuan,Jiang, Hualiang,Chen, Kaixian,Li, Yuanchao,Zhou, Bing,Zhang, Naixia,Yang, Yaxi,Luo, Cheng
supporting information, p. 8503 - 8519 (2016/09/28)
Leukemia with a mixed lineage leukemia (MLL) rearrangement, which harbors a variety of MLL fusion proteins, has a poor prognosis despite the latest improved treatment options. Menin has been reported to be a required cofactor for the leukemogenic activity of MLL fusion proteins. Thus, the disruption of the protein-protein interactions between menin and MLL represents a very promising strategy for curing MLL leukemia. Making use of menin-MLL inhibitors with a shape-based scaffold hopping approach, we have discovered that the antidiarrheal loperamide displays previously unreported mild inhibition for the menin-MLL interaction (IC50 = 69 ± 3 μM). In an effort to repurpose this drug, a series of chemical modification analyses was performed, and three of the loperamide-based analogues, DC-YM21, DC-YM25 and DC-YM26 displayed better activities with IC50 values of 0.83 ± 0.13 μM, 0.69 ± 0.07 μM and 0.66 ± 0.05 μM, respectively. Further treatment with DC-YM21 demonstrated potent and selective blockage of proliferation and induction of both cell cycle arrest and differentiation of leukemia cells harboring MLL translocations, which confirmed the specific mechanism of action. In conclusion, molecules of a novel scaffold targeting menin-MLL interactions were reported and they may serve as new potential therapeutic agents for MLL leukemia.
