Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1089/jop.2017.0023 http://scihub22266oqcxt.onion/10.1089/jop.2017.0023 C5963640!5963640 !28609185     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28609185 &cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 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 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 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28609185 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Ocul+Pharmacol+Ther 2018 ; 34 (1-2 ): 40-51 Nephropedia Template TP {{tp|p=28609185 |t=2018. Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma |pdf=|usr=}}{{28609185 }} gab.com Text Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma JO: J Ocul Pharmacol Ther http://www.kidney.de/pget.php?&tw=1&pmid=28609185 #FOAvip PURPOSE: Rho-associated protein kinase (ROCK) inhibitors lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM). The preclinical characterization of netarsudil, a new ROCK/norepinephrine transporter (NET) inhibitor currently in clinical development, is presented herein. METHODS: The kinase inhibitory activity of netarsudil was compared to its esterase metabolite, netarsudil-M1, and 3 other ROCK inhibitors using a commercially available kinase assay kit. Disruption of actin stress fibers was measured in primary porcine TM cells and disruption of focal adhesions in transformed human TM (HTM) cells. Induction of fibrosis markers after exposure to transforming growth factor-?2 (TGF-?2) was conducted in primary HTM cells. Ocular hypotensive activity and tolerability of topical formulations were evaluated in normotensive Dutch Belted rabbits and Formosan Rock monkeys. In vitro corneal metabolism assays were conducted using dog, pig, rabbit, monkey, and human corneas. In vivo ocular pharmacokinetics was studied in Dutch Belted rabbits. RESULTS: Netarsudil inhibited kinases ROCK1 and ROCK2 with a K(i) of 1?nM each, disrupted actin stress fibers and focal adhesions in TM cells with IC(50)s of 79 and 16?nM, respectively, and blocked the profibrotic effects of TGF-?2 in HTM cells. Netarsudil produced large reductions in IOP in rabbits and monkeys that were sustained for at least 24?h after once daily dosing, with transient, mild hyperemia observed as the only adverse effect. CONCLUSION: Netarsudil is a novel ROCK/NET inhibitor with high potency in biochemical and cell-based assays, an ability to produce large and durable IOP reductions in animal models, and favorable pharmacokinetic and ocular tolerability profiles. Twit Text FOAVip Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma ????J Ocul Pharmacol Ther http://www.kidney.de/pget.php?&tw=1&pmid=28609185 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28609185 #FOAvip English Wikipedia <ref>{{Cite pmid|28609185 }}</ref> Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma #MMPMID28609185 Lin CW ; Sherman B ; Moore LA ; Laethem CL ; Lu DW ; Pattabiraman PP ; Rao PV ; deLong MA ; Kopczynski CC J Ocul Pharmacol Ther 2018[Jan]; 34 (1-2 ): 40-51 PMID28609185 show ga PURPOSE: Rho-associated protein kinase (ROCK) inhibitors lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM). The preclinical characterization of netarsudil, a new ROCK/norepinephrine transporter (NET) inhibitor currently in clinical development, is presented herein. METHODS: The kinase inhibitory activity of netarsudil was compared to its esterase metabolite, netarsudil-M1, and 3 other ROCK inhibitors using a commercially available kinase assay kit. Disruption of actin stress fibers was measured in primary porcine TM cells and disruption of focal adhesions in transformed human TM (HTM) cells. Induction of fibrosis markers after exposure to transforming growth factor-?2 (TGF-?2) was conducted in primary HTM cells. Ocular hypotensive activity and tolerability of topical formulations were evaluated in normotensive Dutch Belted rabbits and Formosan Rock monkeys. In vitro corneal metabolism assays were conducted using dog, pig, rabbit, monkey, and human corneas. In vivo ocular pharmacokinetics was studied in Dutch Belted rabbits. RESULTS: Netarsudil inhibited kinases ROCK1 and ROCK2 with a K(i) of 1?nM each, disrupted actin stress fibers and focal adhesions in TM cells with IC(50)s of 79 and 16?nM, respectively, and blocked the profibrotic effects of TGF-?2 in HTM cells. Netarsudil produced large reductions in IOP in rabbits and monkeys that were sustained for at least 24?h after once daily dosing, with transient, mild hyperemia observed as the only adverse effect. CONCLUSION: Netarsudil is a novel ROCK/NET inhibitor with high potency in biochemical and cell-based assays, an ability to produce large and durable IOP reductions in animal models, and favorable pharmacokinetic and ocular tolerability profiles. |*Drug Discovery [MESH] |Animals [MESH] |Antihypertensive Agents/administration & dosage/chemistry/*therapeutic use [MESH] |Benzoates/administration & dosage/chemistry/*pharmacology [MESH] |Disease Models, Animal [MESH] |Dogs [MESH] |Drug Tolerance [MESH] |Haplorhini [MESH] |Humans [MESH] |Male [MESH] |Molecular Structure [MESH] |Ocular Hypertension/*drug therapy/pathology [MESH] |Ophthalmic Solutions/administration & dosage/chemistry/*therapeutic use [MESH] |Rabbits [MESH] |Swine [MESH]Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hy(epmc).pdf DeepDyve Pubget Overpricing