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10.1016/j.ajpath.2014.04.002 http://scihub22266oqcxt.onion/10.1016/j.ajpath.2014.04.002 C4076560!4076560!24819961     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Am+J+Pathol 2014 ; 184 (7): 2111-22 Nephropedia Template TP {{tp|p=24819961|t=2014. Identification and Characterization of a Novel Small-Molecule Inhibitor of ?-Catenin Signaling |pdf=|usr=}}{{24819961}} gab.com Text Identification and Characterization of a Novel Small-Molecule Inhibitor of -Catenin Signaling JO: Am J Pathol http://www.kidney.de/pget.php?&tw=1&pmid=24819961 #FOAvip Hepatocellular carcinoma (HCC), the third most common cause of cancer-related deaths worldwide, lacks effective medical therapy. Large subsets of HCC demonstrate Wnt/?-catenin activation, making this an attractive therapeutic target. We report strategy and characterization of a novel small-molecule inhibitor, ICG-001, known to affect Wnt signaling by disrupting ?-catenin?CREB binding protein interactions. We queried the ZINC online database for structural similarity to ICG-001 and identified PMED-1 as the lead compound, with ?70% similarity to ICG-001. PMED-1 significantly reduced ?-catenin activity in hepatoblastoma and several HCC cells, as determined by TOPflash reporter assay, with an IC50 ranging from 4.87 to 32 ?mol/L. Although no toxicity was observed in primary human hepatocytes, PMED-1 inhibited Wnt target expression in HCC cells, including those with CTNNB1 mutations, and impaired cell proliferation and viability. PMED-1 treatment decreased ?-catenin?CREB binding protein interactions without affecting total ?-catenin levels or activity of other common kinases. PMED-1 treatment of Tg(OTM:d2EGFP) zebrafish expressing GFP under the ?-catenin/Tcf reporter led to a notable decrease in ?-catenin activity. The PMED effect on ?-catenin signaling lasted from 12 to 24 hours in vitro and 6 to 15 hours in vivo. Thus, using a rapid and cost-effective computational methodology, we have identified a novel and specific small-molecule inhibitor of Wnt signaling that may have implications for HCC treatment. Twit Text FOAVip Identification and Characterization of a Novel Small-Molecule Inhibitor of -Catenin Signaling ????Am J Pathol http://www.kidney.de/pget.php?&tw=1&pmid=24819961 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24819961 #FOAvip English Wikipedia <ref>{{Cite pmid|24819961}}</ref> Identification and Characterization of a Novel Small-Molecule Inhibitor of ?-Catenin Signaling #MMPMID24819961 Delgado ER; Yang J; So J; Leimgruber S; Kahn M; Ishitani T; Shin D; Mustata Wilson G; Monga SP Am J Pathol 2014[Jul]; 184 (7): 2111-22 PMID24819961show ga Hepatocellular carcinoma (HCC), the third most common cause of cancer-related deaths worldwide, lacks effective medical therapy. Large subsets of HCC demonstrate Wnt/?-catenin activation, making this an attractive therapeutic target. We report strategy and characterization of a novel small-molecule inhibitor, ICG-001, known to affect Wnt signaling by disrupting ?-catenin?CREB binding protein interactions. We queried the ZINC online database for structural similarity to ICG-001 and identified PMED-1 as the lead compound, with ?70% similarity to ICG-001. PMED-1 significantly reduced ?-catenin activity in hepatoblastoma and several HCC cells, as determined by TOPflash reporter assay, with an IC50 ranging from 4.87 to 32 ?mol/L. Although no toxicity was observed in primary human hepatocytes, PMED-1 inhibited Wnt target expression in HCC cells, including those with CTNNB1 mutations, and impaired cell proliferation and viability. PMED-1 treatment decreased ?-catenin?CREB binding protein interactions without affecting total ?-catenin levels or activity of other common kinases. PMED-1 treatment of Tg(OTM:d2EGFP) zebrafish expressing GFP under the ?-catenin/Tcf reporter led to a notable decrease in ?-catenin activity. The PMED effect on ?-catenin signaling lasted from 12 to 24 hours in vitro and 6 to 15 hours in vivo. Thus, using a rapid and cost-effective computational methodology, we have identified a novel and specific small-molecule inhibitor of Wnt signaling that may have implications for HCC treatment. äIdentification and Characterization of a Novel Small-Molecule Inhibito(epmc).pdf DeepDyve Pubget Overpricing