- Novel inhibitors of nicotinamide-n-methyltransferase for the treatment of metabolic disorders
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Nicotinamide-N-methyltransferase (NNMT) is a cytosolic enzyme catalyzing the transfer of a methyl group from S-adenosyl-methionine (SAM) to nicotinamide (Nam). It is expressed in many tissues including the liver, adipose tissue, and skeletal muscle. Its expression in several cancer cell lines has been widely discussed in the literature, and recent work established a link between NNMT expression and metabolic diseases. Here we describe our approach to identify potent small molecule inhibitors of NNMT featuring different binding modes as elucidated by X-ray crystallographic studies.
- Czech, Joerg,Dhakshinamoorthy, Saravanakumar,Hallur, Mahanandeesha S.,Kannt, Aimo,Kristam, Rajendra,Rajagopal, Sridharan,Ruf, Sven,Schreuder, Herman,Swamy, Indu,Zech, Gernot
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- Cobalt-catalyzed borylation of aryl halides and pseudohalides
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We report the first Co-catalyzed borylation of aryl halides and pseudohalides with bis(pinacolato)diboron (B2pin2). The synthesis of two new Co(II) complexes of oxazolinylferrocenylphosphine ligands is described. Upon activation with LiMe, the Co complex catalyzes the borylation reactions of aryl bromides, iodides, sulfonates, arenediazonium salts, and even aryl chlorides under mild conditions, providing the borylated products in excellent to moderate yields and with high functional group tolerance.
- Yao, Wubing,Fang, Huaquan,Peng, Sihan,Wen, Huanan,Zhang, Lei,Hu, Aiguo,Huang, Zheng
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- Design, synthesis and biological evaluation of pyrazolo[3,4-d]pyrimidine-based protein kinase D inhibitors
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The multiple roles of protein kinase D (PKD) in various cancer hallmarks have been repeatedly reported. Therefore, the search for novel PKD inhibitors and their evaluation as antitumor agents has gained considerable attention. In this work, novel pyrazolo[3,4-d]pyrimidine based pan-PKD inhibitors with structural variety at position 1 were synthesized and evaluated for biological activity. Starting from 3-IN-PP1, a known PKD inhibitor with IC50 values in the range of 94–108 nM, compound 17m was identified with an improved biochemical inhibitory activity against PKD (IC50 = 17–35 nM). Subsequent cellular assays demonstrated that 3-IN-PP1 and 17m inhibited PKD-dependent cortactin phosphorylation. Furthermore, 3-IN-PP1 displayed potent anti-proliferative activity against PANC-1 cells. Finally, a screening against different cancer cell lines demonstrated that 3-IN-PP1 is a potent and versatile antitumoral agent.
- Gilles, Philippe,Kashyap, Rudra S.,Freitas, Maria Jo?o,Ceusters, Sam,Van Asch, Koen,Janssens, Anke,De Jonghe, Steven,Persoons, Leentje,Cobbaut, Mathias,Daelemans, Dirk,Van Lint, Johan,Voet, Arnout R.D.,De Borggraeve, Wim M.
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supporting information
(2020/08/25)
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- Novel Electron Transport Material for Organic Emitting Diodes
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Some embodiments provide a compound represented by Formula 1, wherein ET1, ET2 and ET3 are optionally substituted quinolinyl or optionally substituted quinoxalinyl; and wherein R1, R2, and R3 are independently selected from the group consisting of H, C1-3 alkyl, and C1-3 perfluoroalkyl. Other embodiments provide an organic electron transmission element and an organic light-emitting diode device comprising a compound of Formula 1.
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