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10.1021/ml500059y http://scihub22266oqcxt.onion/10.1021/ml500059y C4160750!4160750!25221649     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 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 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 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 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       ACS+Med+Chem+Lett 2014 ; 5 (9): 963-7 Nephropedia Template TP {{tp|p=25221649|t=2014. Hydroxybenzothiophene Ketones Are Efficient Pre-mRNA Splicing Modulators Due to Dual Inhibition of Dyrk1A and Clk1/4 |pdf=|usr=}}{{25221649}} gab.com Text Hydroxybenzothiophene Ketones Are Efficient Pre-mRNA Splicing Modulators Due to Dual Inhibition of Dyrk1A and Clk1/4 JO: ACS Med Chem Lett http://www.kidney.de/pget.php?&tw=1&pmid=25221649 #FOAvip Dysregulated usage of pre-mRNA splicing sites contributes to the progression of cancer, neurodegenerative diseases, and viral infections. Serine/arginine-rich (SR) proteins play major roles in the splice site recognition and are largely regulated by phosphorylation. This provides an option for the pharmacological correction of aberrant splicing by inhibiting the relevant kinases. Cdc2-like kinases (Clks) and dual specificity tyrosine phosphorylation-regulated kinases (Dyrks) were both reported to phosphorylate numerous SR proteins in vitro and in vivo. In this study, we describe the discovery of new selective dual Clk/Dyrk1A/1B inhibitors, which are able to modulate alternative pre-mRNA splicing of model gene transcripts in cells with submicromolar potencies. The optimization process yielded a dual Clk and Dyrk inhibitor with exceptionally high ligand efficiency. Our results suggested that dual inhibition of both Clk1 and Dyrk1A increased the efficacy of pre-mRNA splicing modulation. Twit Text FOAVip Hydroxybenzothiophene Ketones Are Efficient Pre-mRNA Splicing Modulators Due to Dual Inhibition of Dyrk1A and Clk1/4 ????ACS Med Chem Lett http://www.kidney.de/pget.php?&tw=1&pmid=25221649 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25221649 #FOAvip English Wikipedia <ref>{{Cite pmid|25221649}}</ref> Hydroxybenzothiophene Ketones Are Efficient Pre-mRNA Splicing Modulators Due to Dual Inhibition of Dyrk1A and Clk1/4 #MMPMID25221649 Schmitt C; Miralinaghi P; Mariano M; Hartmann RW; Engel M ACS Med Chem Lett 2014[Sep]; 5 (9): 963-7 PMID25221649show ga Dysregulated usage of pre-mRNA splicing sites contributes to the progression of cancer, neurodegenerative diseases, and viral infections. Serine/arginine-rich (SR) proteins play major roles in the splice site recognition and are largely regulated by phosphorylation. This provides an option for the pharmacological correction of aberrant splicing by inhibiting the relevant kinases. Cdc2-like kinases (Clks) and dual specificity tyrosine phosphorylation-regulated kinases (Dyrks) were both reported to phosphorylate numerous SR proteins in vitro and in vivo. In this study, we describe the discovery of new selective dual Clk/Dyrk1A/1B inhibitors, which are able to modulate alternative pre-mRNA splicing of model gene transcripts in cells with submicromolar potencies. The optimization process yielded a dual Clk and Dyrk inhibitor with exceptionally high ligand efficiency. Our results suggested that dual inhibition of both Clk1 and Dyrk1A increased the efficacy of pre-mRNA splicing modulation. äHydroxybenzothiophene Ketones Are Efficient Pre-mRNA Splicing Modulato(epmc).pdf DeepDyve Pubget Overpricing