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10.1371/journal.pone.0186587 http://scihub22266oqcxt.onion/10.1371/journal.pone.0186587 C5655428!5655428!29065190     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 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 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       PLoS+One 2017 ; 12 (10): ä Nephropedia Template TP {{tp|p=29065190|t=2017. Discovery and pharmacological characterization of a new class of prolyl-tRNA synthetase inhibitor for anti-fibrosis therapy |pdf=|usr=}}{{29065190}} gab.com Text Discovery and pharmacological characterization of a new class of prolyl-tRNA synthetase inhibitor for anti-fibrosis therapy JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=29065190 #FOAvip Scleroderma has clinical characteristics including skin and other tissue fibrosis, but there is an unmet need for anti-fibrotic therapy. Halofuginone (HF) is a well-known anti-fibrosis agent in preclinical and clinical studies which exerts its effect via inhibition of TGF-?/Smad3 signaling pathway. Recently, prolyl-tRNA synthetase (PRS) was elucidated as a target protein for HF that binds to the proline binding site of the catalytic domain of PRS. Here, we characterized a new class of PRS inhibitor (T-3833261) that is carefully designed in a way that binds to the ATP site of the catalytic domain and does not disrupt binding of proline. The anti-fibrotic activity and the mechanism of action for T-3833261 on TGF-?-induced fibrotic assay were compared with those of HF in primary human skin fibroblast. We evaluated in vivo effect of topical application of T-3833261 and HF on TGF-?-induced fibrotic genes expression in mice. We found that T-3833261 suppressed TGF-?-induced ?-smooth muscle actin (?-SMA) and type I collagen ?1 (COL1A1) expression through the Smad3 axis in a similar fashion to HF. In vivo topical application of T-3833261 reduced the increase of fibrotic genes expression such as ?-Sma, Col1a1 and Col1a2 by TGF-? intradermal injection to the ear of a mouse. We revealed that T-3833261 is more effective than HF under the conditions of high proline concentration, as reported in fibrotic tissues. These results suggest the potential of ATP competitive PRS inhibitors for the treatment of fibrotic diseases such as scleroderma. Twit Text FOAVip Discovery and pharmacological characterization of a new class of prolyl-tRNA synthetase inhibitor for anti-fibrosis therapy ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=29065190 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29065190 #FOAvip English Wikipedia <ref>{{Cite pmid|29065190}}</ref> Discovery and pharmacological characterization of a new class of prolyl-tRNA synthetase inhibitor for anti-fibrosis therapy #MMPMID29065190 Shibata A; Kuno M; Adachi R; Sato Y; Hattori H; Matsuda A; Okuzono Y; Igaki K; Tominari Y; Takagi T; Yabuki M; Okaniwa M PLoS One 2017[]; 12 (10): ä PMID29065190show ga Scleroderma has clinical characteristics including skin and other tissue fibrosis, but there is an unmet need for anti-fibrotic therapy. Halofuginone (HF) is a well-known anti-fibrosis agent in preclinical and clinical studies which exerts its effect via inhibition of TGF-?/Smad3 signaling pathway. Recently, prolyl-tRNA synthetase (PRS) was elucidated as a target protein for HF that binds to the proline binding site of the catalytic domain of PRS. Here, we characterized a new class of PRS inhibitor (T-3833261) that is carefully designed in a way that binds to the ATP site of the catalytic domain and does not disrupt binding of proline. The anti-fibrotic activity and the mechanism of action for T-3833261 on TGF-?-induced fibrotic assay were compared with those of HF in primary human skin fibroblast. We evaluated in vivo effect of topical application of T-3833261 and HF on TGF-?-induced fibrotic genes expression in mice. We found that T-3833261 suppressed TGF-?-induced ?-smooth muscle actin (?-SMA) and type I collagen ?1 (COL1A1) expression through the Smad3 axis in a similar fashion to HF. In vivo topical application of T-3833261 reduced the increase of fibrotic genes expression such as ?-Sma, Col1a1 and Col1a2 by TGF-? intradermal injection to the ear of a mouse. We revealed that T-3833261 is more effective than HF under the conditions of high proline concentration, as reported in fibrotic tissues. These results suggest the potential of ATP competitive PRS inhibitors for the treatment of fibrotic diseases such as scleroderma. äDiscovery and pharmacological characterization of a new class of proly(epmc).pdf DeepDyve Pubget Overpricing