- Disrupting the Conserved Salt Bridge in the Trimerization of Influenza A Nucleoprotein
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Antiviral drug resistance in influenza infections has been a major threat to public health. To develop a broad-spectrum inhibitor of influenza to combat the problem of drug resistance, we previously identified the highly conserved E339?R416 salt bridge of the nucleoprotein trimer as a target and compound 1 as an inhibitor disrupting the salt bridge with an EC50 = 2.7 μM against influenza A (A/WSN/1933). We have further modified this compound via a structure-based approach and performed antiviral activity screening to identify compounds 29 and 30 with EC50 values of 110 and 120 nM, respectively, and without measurable host cell cytotoxicity. Compared to the clinically used neuraminidase inhibitors, these two compounds showed better activity profiles against drug-resistant influenza A strains, as well as influenza B, and improved survival of influenza-infected mice.
- Woodring, Jennifer L.,Lu, Shao-Hung,Krasnova, Larissa,Wang, Shih-Chi,Chen, Jhih-Bin,Chou, Chiu-Chun,Huang, Yi-Chou,Cheng, Ting-Jen Rachel,Wu, Ying-Ta,Chen, Yu-Hou,Fang, Jim-Min,Tsai, Ming-Daw,Wong, Chi-Huey
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p. 205 - 215
(2020/01/02)
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- Chemical screening of novel strigolactone agonists that specifically interact with DWARF14 protein
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Strigolactones (SLs) are a class of plant hormones that regulate shoot branching as well as being known as root-derived signals for parasitic and symbiotic interactions. The physical interaction between SLs and the DWARF14 (D14) receptor family can be examined by differential scanning fluorimetry (DSF) that monitors the changes in protein melting temperature (Tm). The Tm of D14 is lowered by bioactive SLs in DSF analysis. In this report, we screened the compounds that lower the Tm of Arabidopsis D14 (AtD14) as potential candidates for SL agonists using DSF analysis. Subsequent physiological analyzes revealed that 113D10 acts as a novel SL agonist in a D14-dependent manner. Intriguingly, 113D10 has a chemical structure different from natural SLs in that it does not possess an enol ether bond that connects to a methylbutenolide moiety. Moreover, 113D10 does not stimulate seed germination of root parasitic plants. Accordingly, 113D10 can be a useful tool for SL studies and agricultural applications.
- Yasui, Rei,Seto, Yoshiya,Ito, Shinsaku,Kawada, Kojiro,Itto-Nakama, Kaori,Mashiguchi, Kiyoshi,Yamaguchi, Shinjiro
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supporting information
p. 938 - 942
(2019/02/09)
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- SUBSTITUTED THIAZOL-2-YLAMINE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE AS 11-BETA HSD1 MODULATORS
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The present invention is directed to substituted thiazol-2-ylamine derivatives and pharmaceutically acceptable salts thereof that inhibit 11βHSD1 and that may be useful in the treatment of diseases in which modulation or inhibition of 11βHSD1 is beneficial or where a reduction in intracellular glucorticoid levels is desirable. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases, disorders, or conditions in which modulation or inhibition of 11βHSD1 is beneficial or where a reduction in intracellular glucorticoid levels is desirable.
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Page/Page column 9
(2012/02/06)
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