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10.3390/ph15020204 http://scihub22266oqcxt.onion/10.3390/ph15020204 35215314!8880557!35215314     free     free     free Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Pharmaceuticals+(Basel) 2022 ; 15 (2): ä Nephropedia Template TP {{tp|p=35215314|t=2022. The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation |pdf=|usr=}}{{35215314}} gab.com Text The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation JO: Pharmaceuticals (Basel) http://www.kidney.de/pget.php?&tw=1&pmid=35215314 #FOAvip The diverse modes of action of small molecule inhibitors provide versatile tools to investigate basic biology and develop therapeutics. However, it remains a challenging task to evaluate their exact mechanisms of action. We identified two classes of inhibitors for the p97 ATPase: ATP competitive and allosteric. We showed that the allosteric p97 inhibitor, UPCDC-30245, does not affect two well-known cellular functions of p97, endoplasmic-reticulum-associated protein degradation and the unfolded protein response pathway; instead, it strongly increases the lipidated form of microtubule-associated proteins 1A/1B light chain 3B (LC3-II), suggesting an alteration of autophagic pathways. To evaluate the molecular mechanism, we performed proteomic analysis of UPCDC-30245 treated cells. Our results revealed that UPCDC-30245 blocks endo-lysosomal degradation by inhibiting the formation of early endosome and reducing the acidity of the lysosome, an effect not observed with the potent p97 inhibitor CB-5083. This unique effect allows us to demonstrate UPCDC-30245 exhibits antiviral effects against coronavirus by blocking viral entry. Twit Text FOAVip The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation ????Pharmaceuticals (Basel) http://www.kidney.de/pget.php?&tw=1&pmid=35215314 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=35215314 #FOAvip English Wikipedia <ref>{{Cite pmid|35215314}}</ref> The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation #MMPMID35215314 Wang F; Li S; Cheng KW; Rosencrans WM; Chou TF Pharmaceuticals (Basel) 2022[Feb]; 15 (2): ä PMID35215314show ga The diverse modes of action of small molecule inhibitors provide versatile tools to investigate basic biology and develop therapeutics. However, it remains a challenging task to evaluate their exact mechanisms of action. We identified two classes of inhibitors for the p97 ATPase: ATP competitive and allosteric. We showed that the allosteric p97 inhibitor, UPCDC-30245, does not affect two well-known cellular functions of p97, endoplasmic-reticulum-associated protein degradation and the unfolded protein response pathway; instead, it strongly increases the lipidated form of microtubule-associated proteins 1A/1B light chain 3B (LC3-II), suggesting an alteration of autophagic pathways. To evaluate the molecular mechanism, we performed proteomic analysis of UPCDC-30245 treated cells. Our results revealed that UPCDC-30245 blocks endo-lysosomal degradation by inhibiting the formation of early endosome and reducing the acidity of the lysosome, an effect not observed with the potent p97 inhibitor CB-5083. This unique effect allows us to demonstrate UPCDC-30245 exhibits antiviral effects against coronavirus by blocking viral entry. äThe p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation (epmc).pdf DeepDyve Pubget Overpricing