54015-04-2Relevant articles and documents
Discovery of CDK5 Inhibitors through Structure-Guided Approach
Khair, Nishat Z.,Lenjisa, Jimma L.,Tadesse, Solomon,Kumarasiri, Malika,Basnet, Sunita K. C.,Mekonnen, Laychiluh B.,Li, Manjun,Diab, Sarah,Sykes, Matthew J.,Albrecht, Hugo,Milne, Robert,Wang, Shudong
supporting information, p. 786 - 791 (2019/05/17)
Specific abrogation of cyclin-dependent kinase 5 (CDK5) activity has been validated as a viable approach for the development of anticancer agents. However, no selective CDK5 inhibitor has been reported to date. Herein, a structure-based in silico screenin
Discovery of 5-(2-(phenylamino)pyrimidin-4-yl)thiazol-2(3H)-one derivatives as potent Mnk2 inhibitors: Synthesis, SAR analysis and biological evaluation
Diab, Sarah,Teo, Theodosia,Kumarasiri, Malika,Li, Peng,Yu, Mingfeng,Lam, Frankie,Basnet, Sunita K. C.,Sykes, Matthew J.,Albrecht, Hugo,Milne, Robert,Wang, Shudong
, p. 962 - 972 (2014/05/20)
Phosphorylation of eIF4E by human mitogen-activated protein kinase (MAPK)-interacting kinases (Mnks) is crucial for human tumourigenesis and development. Targeting Mnks may provide a novel anticancer therapeutic strategy. However, the lack of selective Mnk inhibitors has so far hampered pharmacological target validation and clinical drug development. Herein, we report, for the first time, the discovery of a series of 5-(2-(phenylamino) pyrimidin-4-yl)thiazole-2(3H)-one derivatives as Mnk inhibitors. Several derivatives demonstrate very potent Mnk2 inhibitory activity. The most active and selective compounds were tested against a panel of cancer cell lines, and the results confirm the cell-type-specific effect of these Mnk inhibitors. Detailed cellular mechanistic studies reveal that Mnk inhibitors are capable of reducing the expression level of anti-apoptotic protein Mcl-1, and of promoting apoptosis in MV4-11 acute myeloid leukaemia cells. Highly active Mnk2 inhibitors: Mnk-related cancer biology is an area of intensive research, but its inhibitor discovery has lagged behind due to a lack of understanding of the protein structure. Herein we report the discovery of Mnk2 inhibitors (e.g. 8 e). These potent and selective inhibitors are extremely valuable for target validation and drug discovery.
Ligustrazine derivatives. Part 6: Design, synthesis and evaluation of novel ligustrazinyl acylguanidine derivatives as potential cardiovascular agents
Li, Zhenyu,Yu, Fang,Zhan, Peng,Shen, Yuemao,Liu, Xinyong,Cui, Lei,Wang, Shouxun
, p. 928 - 933,6 (2020/08/31)
A series of novel Ligustrazinyl acylguanidines was designed, synthesized and evaluated for their protective effect on injured vascular endothelial cell (ECV-304). The preliminary results demonstrated that some compounds possessed more potent activities than that of Ligustrazine in stimulating replication of the injured endothelial cell. Among the active compounds, compounds 8b, 8f and 8l displayed remarkable antioxidative activity with low EC50 values of 0.097, 0.059 and 0.094 mM, respectively. Structure-activity relationships were briefly discussed.