111376-39-7Relevant articles and documents
Novel Propargyl-Linked Bisubstrate Analogues as Tight-Binding Inhibitors for Nicotinamide N-Methyltransferase
Chen, Dongxing,Li, Linjie,Diaz, Krystal,Iyamu, Iredia D.,Yadav, Ravi,Noinaj, Nicholas,Huang, Rong
, p. 10783 - 10797 (2019/12/25)
Nicotinamide N-methyltransferase (NNMT) catalyzes the methyl transfer from the cofactor S-adenosylmethionine to nicotinamide and other pyridine-containing compounds. NNMT is an important regulator for nicotinamide metabolism and methylation potential. Aberrant expression levels of NNMT have been implicated in cancer, metabolic, and neurodegenerative diseases, which makes NNMT a potential therapeutic target. Therefore, potent and selective NNMT inhibitors can serve as valuable tools to investigate the roles of NNMT in its mediated diseases. Here, we applied a rational strategy to design and synthesize the tight-binding bisubstrate inhibitor LL320 through a novel propargyl linker. LL320 demonstrates a Ki value of 1.6 ± 0.3 nM, which is the most potent inhibitor to date. The cocrystal structure of LL320 confirms its interaction with both the substrate and cofactor binding sites on NNMT. Importantly, this is the first example of using the propargyl linker to construct potent methyltransferase inhibitors, which will expand our understanding of the transition state of methyl transfer.
COMPOUNDS AND METHODS for the inhibition of HDAC
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Paragraph 0698-0699, (2015/11/24)
Disclosed are compounds having the formula: wherein X1, X2, X3, R1, R2, R3, R4, Y, A, Z, L and n are as defined herein, and methods of making and using the same.
7-PHENYL-ISOQUINOLINE-5-SULFONYLAMINO DERIVATIVES AS INHIBITORS OF AKT (PROTEINKINASE B)
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Page/Page column 28, (2010/02/12)
The present invention relates to compounds Formula (I) as inhibitors of AKT activity, which are useful for the treatment of susceptible neoplasms and viral infections.