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10.1021/acsmedchemlett.5b00407 http://scihub22266oqcxt.onion/10.1021/acsmedchemlett.5b00407 C5018864!5018864!27660687     free     free     free Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       ACS+Med+Chem+Lett 2016 ; 7 (9): 835-40 Nephropedia Template TP {{tp|p=27660687|t=2016. Polar Recognition Group Study of Keap1-Nrf2 Protein?Protein Interaction Inhibitors |pdf=|usr=}}{{27660687}} gab.com Text Polar Recognition Group Study of Keap1-Nrf2 Protein Protein Interaction Inhibitors JO: ACS Med Chem Lett http://www.kidney.de/pget.php?&tw=1&pmid=27660687 #FOAvip Directly disrupting the Keap1-Nrf2 protein?protein interaction (PPI) has emerged as an attractive way to activate Nrf2, and Keap1-Nrf2 PPI inhibitors have been proposed as potential agents to relieve inflammatory and oxidative stress diseases. In this work, we investigated the diacetic moiety around the potent Keap1-Nrf2 PPI inhibitor DDO1018 (2), which was reported by our group previously. Exploration of bioisosteric replacements afforded the ditetrazole analog 7, which maintains the potent PPI inhibition activity (IC50 = 15.8 nM) in an in vitro fluorescence polarization assay. Physicochemical property determination demonstrated that ditetrazole replacement can improve the drug-like property, including elevation of pKa, log D, and transcellular permeability. Additionally, 7 is more efficacious than 2 on inducing the expression of Nrf2-dependent gene products in cells. This study provides an alternative way to replace the diacetic moiety and occupy the polar subpockets in Keap1, which can benefit the subsequent development of Keap1-Nrf2 PPI inhibitor. Twit Text FOAVip Polar Recognition Group Study of Keap1-Nrf2 Protein Protein Interaction Inhibitors ????ACS Med Chem Lett http://www.kidney.de/pget.php?&tw=1&pmid=27660687 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27660687 #FOAvip English Wikipedia <ref>{{Cite pmid|27660687}}</ref> Polar Recognition Group Study of Keap1-Nrf2 Protein?Protein Interaction Inhibitors #MMPMID27660687 Lu MC; Tan SJ; Ji JA; Chen ZY; Yuan ZW; You QD; Jiang ZY ACS Med Chem Lett 2016[Sep]; 7 (9): 835-40 PMID27660687show ga Directly disrupting the Keap1-Nrf2 protein?protein interaction (PPI) has emerged as an attractive way to activate Nrf2, and Keap1-Nrf2 PPI inhibitors have been proposed as potential agents to relieve inflammatory and oxidative stress diseases. In this work, we investigated the diacetic moiety around the potent Keap1-Nrf2 PPI inhibitor DDO1018 (2), which was reported by our group previously. Exploration of bioisosteric replacements afforded the ditetrazole analog 7, which maintains the potent PPI inhibition activity (IC50 = 15.8 nM) in an in vitro fluorescence polarization assay. Physicochemical property determination demonstrated that ditetrazole replacement can improve the drug-like property, including elevation of pKa, log D, and transcellular permeability. Additionally, 7 is more efficacious than 2 on inducing the expression of Nrf2-dependent gene products in cells. This study provides an alternative way to replace the diacetic moiety and occupy the polar subpockets in Keap1, which can benefit the subsequent development of Keap1-Nrf2 PPI inhibitor. äPolar Recognition Group Study of Keap1-Nrf2 Protein?Protein Interactio(epmc).pdf DeepDyve Pubget Overpricing