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10.18632/oncotarget.15166 http://scihub22266oqcxt.onion/10.18632/oncotarget.15166 C5370004!5370004!28187433     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Oncotarget 2017 ; 8 (10): 16829-42 Nephropedia Template TP {{tp|p=28187433|t=2017. Doxycycline directly targets PAR1 to suppress tumor progression |pdf=|usr=}}{{28187433}} gab.com Text Doxycycline directly targets PAR1 to suppress tumor progression JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=28187433 #FOAvip Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model. Molecular docking and molecular dynamic simulations revealed that doxycycline interacts with key amino acids in PAR1. Mutation of PAR1 further confirmed the computation-based results. Moreover, doxycycline provides highly selective inhibition of PAR1 signaling in tumors in vitro and in vivo. Using pathological clinical samples co-stained for doxycycline and PAR1, it was found that doxycycline fluorescence intensity and PAR1 expression shown a clear positive correlation. Thus, doxycycline may be a useful targeted anti-cancer drug that should be further investigated in clinical trials. Twit Text FOAVip Doxycycline directly targets PAR1 to suppress tumor progression ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=28187433 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28187433 #FOAvip English Wikipedia <ref>{{Cite pmid|28187433}}</ref> Doxycycline directly targets PAR1 to suppress tumor progression #MMPMID28187433 Zhong W; Chen S; Zhang Q; Xiao T; Qin Y; Gu J; Sun B; Liu Y; Jing X; Hu X; Zhang P; Zhou H; Sun T; Yang C Oncotarget 2017[Mar]; 8 (10): 16829-42 PMID28187433show ga Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model. Molecular docking and molecular dynamic simulations revealed that doxycycline interacts with key amino acids in PAR1. Mutation of PAR1 further confirmed the computation-based results. Moreover, doxycycline provides highly selective inhibition of PAR1 signaling in tumors in vitro and in vivo. Using pathological clinical samples co-stained for doxycycline and PAR1, it was found that doxycycline fluorescence intensity and PAR1 expression shown a clear positive correlation. Thus, doxycycline may be a useful targeted anti-cancer drug that should be further investigated in clinical trials. äDoxycycline directly targets PAR1 to suppress tumor progression (epmc).pdf DeepDyve Pubget Overpricing