Sandbox Reserved 1170 - Revision history

http://52.214.119.220/wiki/index.php?action=history&feed=atom&title=Sandbox_Reserved_1170 Sandbox Reserved 1170 - Revision history 2026-04-05T06:34:57Z Revision history for this page on the wiki MediaWiki 1.11.2 http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1170&diff=2587736&oldid=prev Whitney Hart at 02:49, 19 April 2016 2016-04-19T02:49:18Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 02:49, 19 April 2016</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 16:</td> <td colspan="2" class="diff-lineno">Line 16:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== ECL2 ===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== ECL2 ===</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>hGPR40 contains a highly conserved hairpin extracellular loop. This extracellular loop (<scene name='72/721541/Ecl2/4'>ECL2</scene>) is the longest and most divergent of the extracellular loops found in proteins (<scene name='72/721541/Ecl2_top/<del style="color: red; font-weight: bold; text-decoration: none;">1</del>'>top view of ECL2</scene>). The loop is accompanied by a [https://en.wikibooks.org/wiki/Structural_Biochemistry/Chemical_Bonding/_Disulfide_bonds disulfide bond] (<scene name='72/721541/Cysteine_bridge/3'>Cys79 and Cys170</scene>) that forms between transmembrane helix 4 and the C-terminus of the ECL2 loop. In hGPR40, ECL2 has two sections: a <FONT COLOR="#00FFFF">'''beta sheet'''</FONT> and an <FONT COLOR="#FF00FF">'''auxiliary loop'''</FONT>. The [https://en.wikipedia.org/wiki/Beta_sheet beta sheet] spans helices 4 and 5 and is shorter in hGPR40 than in other GPCRs. The ECL2 of hGPR40 also differs from that of other proteins because it contains an auxiliary loop of 13 extra residues. The entire extracellular loop has low mobility and flexibility which allows it to act as a cap for the binding pocket. The only exception to the low flexibility is the tip of the auxiliary loop, which corresponds to residues Asp152-Asn155. This area of greater mobility allows for substrates to enter the binding site.<ref name="Srivastava"/></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>hGPR40 contains a highly conserved hairpin extracellular loop. This extracellular loop (<scene name='72/721541/Ecl2/4'>ECL2</scene>) is the longest and most divergent of the extracellular loops found in proteins (<scene name='72/721541/Ecl2_top/<ins style="color: red; font-weight: bold; text-decoration: none;">2</ins>'>top view of ECL2</scene>). The loop is accompanied by a [https://en.wikibooks.org/wiki/Structural_Biochemistry/Chemical_Bonding/_Disulfide_bonds disulfide bond] (<scene name='72/721541/Cysteine_bridge/3'>Cys79 and Cys170</scene>) that forms between transmembrane helix 4 and the C-terminus of the ECL2 loop. In hGPR40, ECL2 has two sections: a <FONT COLOR="#00FFFF">'''beta sheet'''</FONT> and an <FONT COLOR="#FF00FF">'''auxiliary loop'''</FONT>. The [https://en.wikipedia.org/wiki/Beta_sheet beta sheet] spans helices 4 and 5 and is shorter in hGPR40 than in other GPCRs. The ECL2 of hGPR40 also differs from that of other proteins because it contains an auxiliary loop of 13 extra residues. The entire extracellular loop has low mobility and flexibility which allows it to act as a cap for the binding pocket. The only exception to the low flexibility is the tip of the auxiliary loop, which corresponds to residues Asp152-Asn155. This area of greater mobility allows for substrates to enter the binding site.<ref name="Srivastava"/></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Function ==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Function ==</div></td></tr> </table>

Whitney Hart http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1170&diff=2587724&oldid=prev Whitney Hart at 02:15, 19 April 2016 2016-04-19T02:15:14Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 02:15, 19 April 2016</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 16:</td> <td colspan="2" class="diff-lineno">Line 16:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== ECL2 ===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== ECL2 ===</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>hGPR40 contains a highly conserved hairpin extracellular loop. This extracellular loop (<scene name='72/721541/Ecl2/<del style="color: red; font-weight: bold; text-decoration: none;">3</del>'>ECL2</scene>) is the longest and most divergent of the extracellular loops found in proteins. The loop is accompanied by a [https://en.wikibooks.org/wiki/Structural_Biochemistry/Chemical_Bonding/_Disulfide_bonds disulfide bond] (<scene name='72/721541/Cysteine_bridge/3'>Cys79 and Cys170</scene>) that forms between transmembrane helix 4 and the C-terminus of the ECL2 loop. In hGPR40, ECL2 has two sections: a <FONT COLOR="#00FFFF">'''beta sheet'''</FONT> and an <FONT COLOR="#FF00FF">'''auxiliary loop'''</FONT>. The [https://en.wikipedia.org/wiki/Beta_sheet beta sheet] spans helices 4 and 5 and is shorter in hGPR40 than in other GPCRs. The ECL2 of hGPR40 also differs from that of other proteins because it contains an auxiliary loop of 13 extra residues. The entire extracellular loop has low mobility and flexibility which allows it to act as a cap for the binding pocket. The only exception to the low flexibility is the tip of the auxiliary loop, which corresponds to residues Asp152-Asn155. This area of greater mobility allows for substrates to enter the binding site.<ref name="Srivastava"/></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>hGPR40 contains a highly conserved hairpin extracellular loop. This extracellular loop (<scene name='72/721541/Ecl2/<ins style="color: red; font-weight: bold; text-decoration: none;">4</ins>'>ECL2</scene>) is the longest and most divergent of the extracellular loops found in proteins <ins style="color: red; font-weight: bold; text-decoration: none;">(<scene name='72/721541/Ecl2_top/1'>top view of ECL2</scene>)</ins>. The loop is accompanied by a [https://en.wikibooks.org/wiki/Structural_Biochemistry/Chemical_Bonding/_Disulfide_bonds disulfide bond] (<scene name='72/721541/Cysteine_bridge/3'>Cys79 and Cys170</scene>) that forms between transmembrane helix 4 and the C-terminus of the ECL2 loop. In hGPR40, ECL2 has two sections: a <FONT COLOR="#00FFFF">'''beta sheet'''</FONT> and an <FONT COLOR="#FF00FF">'''auxiliary loop'''</FONT>. The [https://en.wikipedia.org/wiki/Beta_sheet beta sheet] spans helices 4 and 5 and is shorter in hGPR40 than in other GPCRs. The ECL2 of hGPR40 also differs from that of other proteins because it contains an auxiliary loop of 13 extra residues. The entire extracellular loop has low mobility and flexibility which allows it to act as a cap for the binding pocket. The only exception to the low flexibility is the tip of the auxiliary loop, which corresponds to residues Asp152-Asn155. This area of greater mobility allows for substrates to enter the binding site.<ref name="Srivastava"/></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Function ==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Function ==</div></td></tr> </table>

Whitney Hart http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1170&diff=2587715&oldid=prev Whitney Hart at 01:52, 19 April 2016 2016-04-19T01:52:35Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 01:52, 19 April 2016</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 27:</td> <td colspan="2" class="diff-lineno">Line 27:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Clinical Relevance ==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Clinical Relevance ==</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>By signaling predominantly through G<sub>aq/11</sub>, hGPR40 increases intracellular calcium and activates phospholipases to generate diacylglycerols resulting in increased insulin secretion. Synthetic small-molecule agonists of <del style="color: red; font-weight: bold; text-decoration: none;">GPR40 </del>enhance insulin secretion in a glucose dependent manner [http://www.merriam-webster.com/medical/in%20vitro in vitro] and [http://www.merriam-webster.com/medical/in%20vivo in vivo] with a mechanism similar to that found with fatty acids. <del style="color: red; font-weight: bold; text-decoration: none;">GPR40 </del>agonists have shown efficacy in increasing insulin secretion and lowering blood glucose in rodent models of type 2 diabetes.<ref name="Burant"/></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>By signaling predominantly through G<sub>aq/11</sub>, hGPR40 increases intracellular calcium and activates phospholipases to generate diacylglycerols resulting in increased insulin secretion. Synthetic small-molecule agonists of <ins style="color: red; font-weight: bold; text-decoration: none;">hGPR40 </ins>enhance insulin secretion in a glucose dependent manner [http://www.merriam-webster.com/medical/in%20vitro in vitro] and [http://www.merriam-webster.com/medical/in%20vivo in vivo] with a mechanism similar to that found with fatty acids. <ins style="color: red; font-weight: bold; text-decoration: none;">hGPR40 </ins>agonists have shown efficacy in increasing insulin secretion and lowering blood glucose in rodent models of type 2 diabetes.<ref name="Burant"/></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== TAK-875 ===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== TAK-875 ===</div></td></tr> </table>

Whitney Hart http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1170&diff=2587714&oldid=prev Whitney Hart at 01:51, 19 April 2016 2016-04-19T01:51:30Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 01:51, 19 April 2016</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 27:</td> <td colspan="2" class="diff-lineno">Line 27:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Clinical Relevance ==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Clinical Relevance ==</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>By signaling predominantly through G<sub>aq/11</sub>, <del style="color: red; font-weight: bold; text-decoration: none;">GPR40 </del>increases intracellular calcium and activates phospholipases to generate diacylglycerols resulting in increased insulin secretion. Synthetic small-molecule agonists of GPR40 enhance insulin secretion in a glucose dependent manner [http://www.merriam-webster.com/medical/in%20vitro in vitro] and [http://www.merriam-webster.com/medical/in%20vivo in vivo] with a mechanism similar to that found with fatty acids. GPR40 agonists have shown efficacy in increasing insulin secretion and lowering blood glucose in rodent models of type 2 diabetes.<ref name="Burant"/></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>By signaling predominantly through G<sub>aq/11</sub>, <ins style="color: red; font-weight: bold; text-decoration: none;">hGPR40 </ins>increases intracellular calcium and activates phospholipases to generate diacylglycerols resulting in increased insulin secretion. Synthetic small-molecule agonists of GPR40 enhance insulin secretion in a glucose dependent manner [http://www.merriam-webster.com/medical/in%20vitro in vitro] and [http://www.merriam-webster.com/medical/in%20vivo in vivo] with a mechanism similar to that found with fatty acids. GPR40 agonists have shown efficacy in increasing insulin secretion and lowering blood glucose in rodent models of type 2 diabetes.<ref name="Burant"/></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== TAK-875 ===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== TAK-875 ===</div></td></tr> </table>

Whitney Hart http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1170&diff=2587709&oldid=prev Whitney Hart at 01:38, 19 April 2016 2016-04-19T01:38:54Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 01:38, 19 April 2016</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 16:</td> <td colspan="2" class="diff-lineno">Line 16:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== ECL2 ===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== ECL2 ===</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>hGPR40 contains a highly conserved hairpin loop. This extracellular loop (<scene name='72/721541/Ecl2/3'>ECL2</scene>) is the longest and most divergent of the extracellular loops found in proteins. The loop is accompanied by a [https://en.wikibooks.org/wiki/Structural_Biochemistry/Chemical_Bonding/_Disulfide_bonds disulfide bond] (<scene name='72/721541/Cysteine_bridge/3'>Cys79 and Cys170</scene>) that forms between transmembrane helix 4 and the C-terminus of the ECL2 loop. In hGPR40, ECL2 has two sections: a <FONT COLOR="#00FFFF">'''beta sheet'''</FONT> and an <FONT COLOR="#FF00FF">'''auxiliary loop'''</FONT>. The [https://en.wikipedia.org/wiki/Beta_sheet beta sheet] spans helices 4 and 5 and is shorter in hGPR40 than in other GPCRs. The ECL2 of hGPR40 also differs from that of other proteins because it contains an auxiliary loop of 13 extra residues. The entire extracellular loop has low mobility and flexibility which allows it to act as a cap for the binding pocket. The only exception to the low flexibility is the tip of the auxiliary loop, which corresponds to residues Asp152-Asn155. This area of greater mobility allows for substrates to enter the binding site.<ref name="Srivastava"/></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>hGPR40 contains a highly conserved hairpin <ins style="color: red; font-weight: bold; text-decoration: none;">extracellular </ins>loop. This extracellular loop (<scene name='72/721541/Ecl2/3'>ECL2</scene>) is the longest and most divergent of the extracellular loops found in proteins. The loop is accompanied by a [https://en.wikibooks.org/wiki/Structural_Biochemistry/Chemical_Bonding/_Disulfide_bonds disulfide bond] (<scene name='72/721541/Cysteine_bridge/3'>Cys79 and Cys170</scene>) that forms between transmembrane helix 4 and the C-terminus of the ECL2 loop. In hGPR40, ECL2 has two sections: a <FONT COLOR="#00FFFF">'''beta sheet'''</FONT> and an <FONT COLOR="#FF00FF">'''auxiliary loop'''</FONT>. The [https://en.wikipedia.org/wiki/Beta_sheet beta sheet] spans helices 4 and 5 and is shorter in hGPR40 than in other GPCRs. The ECL2 of hGPR40 also differs from that of other proteins because it contains an auxiliary loop of 13 extra residues. The entire extracellular loop has low mobility and flexibility which allows it to act as a cap for the binding pocket. The only exception to the low flexibility is the tip of the auxiliary loop, which corresponds to residues Asp152-Asn155. This area of greater mobility allows for substrates to enter the binding site.<ref name="Srivastava"/></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Function ==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Function ==</div></td></tr> </table>

Whitney Hart http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1170&diff=2587356&oldid=prev Jacob Applegarth at 15:52, 15 April 2016 2016-04-15T15:52:01Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 15:52, 15 April 2016</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 33:</td> <td colspan="2" class="diff-lineno">Line 33:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== Other Potential Inhibitors ===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== Other Potential Inhibitors ===</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>[[Image:AMG-837.jpg |300 px|right|thumb|Figure 5. Structure of the potential agonist AMG-837. In clinical trials, this drug was found to increase glucose tolerance in individuals with Type 2 Diabetes.]] TAK-875 had the most promising outlooks out of any current known agonists of hGPR40, but it was discontinued. Some other agonists tested in clinical trials include AMG-837 and AM-1638. When coadministered, AMG-837 (Figure 5) and AM-1638 enhanced glucose tolerance, but they were found to be toxic in the human trials. Some other agonsits are currently being examined as well. One compound, LY 2881835 (Eli Lilly & Company, Indianapolis, IN), has undergone clinical trials, but the results are unknown. In addition to the above-mentioned compound, other orally bioavailable GPR40-specific agonists are currently in preclinical or clinical development. As of 2015, TUG-770 and CNX-011-67 (Connexios Life Sciences, Karnataka, India) were in preclinical trials and JTT-851 (Japan Tobacco, Toyko, Japan), and P11187 (Piramal, Mumbai, India) were in clinical trails. </div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>[[Image:AMG-837.jpg |300 px|right|thumb|Figure 5. Structure of the potential agonist AMG-837. In clinical trials, this drug was found to increase glucose tolerance in individuals with Type 2 Diabetes.]] TAK-875 had the most promising outlooks out of any current known agonists of hGPR40, but it was discontinued. Some other agonists tested in clinical trials include AMG-837 and AM-1638. When coadministered, AMG-837 (Figure 5) and AM-1638 enhanced glucose tolerance, but they were found to be toxic in the human trials. Some other agonsits are currently being examined as well. One compound, LY 2881835 (Eli Lilly & Company, Indianapolis, IN), has undergone clinical trials, but the results are unknown. In addition to the above-mentioned compound, other orally bioavailable GPR40-specific agonists are currently in preclinical or clinical development. As of 2015, TUG-770 and CNX-011-67 (Connexios Life Sciences, Karnataka, India) were in preclinical trials and JTT-851 (Japan Tobacco, Toyko, Japan), and P11187 (Piramal, Mumbai, India) were in clinical trails.<ins style="color: red; font-weight: bold; text-decoration: none;"><ref name="Mancini">PMID: 25604916</ref> </ins></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> </table>

Jacob Applegarth http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1170&diff=2587355&oldid=prev Whitney Hart at 15:51, 15 April 2016 2016-04-15T15:51:41Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 15:51, 15 April 2016</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 33:</td> <td colspan="2" class="diff-lineno">Line 33:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== Other Potential Inhibitors ===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== Other Potential Inhibitors ===</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>[[Image:AMG-837.jpg |300 px|right|thumb|Figure 5. Structure of the potential agonist AMG-837. In clinical trials, this drug was found to increase glucose tolerance in individuals with Type 2 Diabetes.]] TAK-875 had the most promising outlooks out of any current known agonists of hGPR40, but it was discontinued. Some other agonists tested in clinical trials include AMG-837 and AM-1638. When coadministered, AMG-837 (Figure 5) and AM-1638 enhanced glucose tolerance, but they were found to be toxic in the human trials. Some other agonsits are currently being examined as well. One compound, LY 2881835, has undergone clinical trials, but the results are unknown. In addition to the above-mentioned compound, other orally bioavailable GPR40-specific agonists are currently in preclinical or clinical development. As of 2015, TUG-770 and CNX-011-67 (Connexios Life Sciences, Karnataka, India) were in preclinical trials and JTT-851 (Japan Tobacco, Toyko, Japan), and P11187 (Piramal, Mumbai, India) were in clinical trails. </div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>[[Image:AMG-837.jpg |300 px|right|thumb|Figure 5. Structure of the potential agonist AMG-837. In clinical trials, this drug was found to increase glucose tolerance in individuals with Type 2 Diabetes.]] TAK-875 had the most promising outlooks out of any current known agonists of hGPR40, but it was discontinued. Some other agonists tested in clinical trials include AMG-837 and AM-1638. When coadministered, AMG-837 (Figure 5) and AM-1638 enhanced glucose tolerance, but they were found to be toxic in the human trials. Some other agonsits are currently being examined as well. One compound, LY 2881835 <ins style="color: red; font-weight: bold; text-decoration: none;">(Eli Lilly & Company, Indianapolis, IN)</ins>, has undergone clinical trials, but the results are unknown. In addition to the above-mentioned compound, other orally bioavailable GPR40-specific agonists are currently in preclinical or clinical development. As of 2015, TUG-770 and CNX-011-67 (Connexios Life Sciences, Karnataka, India) were in preclinical trials and JTT-851 (Japan Tobacco, Toyko, Japan), and P11187 (Piramal, Mumbai, India) were in clinical trails. </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> </table>

Whitney Hart http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1170&diff=2587354&oldid=prev Whitney Hart at 15:50, 15 April 2016 2016-04-15T15:50:16Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 15:50, 15 April 2016</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 33:</td> <td colspan="2" class="diff-lineno">Line 33:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== Other Potential Inhibitors ===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== Other Potential Inhibitors ===</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>TAK-875 had the most promising outlooks out of any current known agonists of hGPR40, but it was discontinued. Some other agonists tested in clinical trials include AMG-837 and AM-1638. When coadministered, AMG-837 and AM-1638 enhanced glucose tolerance, but they were found to be toxic in the human trials. Some other agonsits are currently being examined as well. One compound, LY 2881835, has undergone clinical trials, but the results are unknown. In addition to the above-mentioned compound, other orally bioavailable GPR40-specific agonists are currently in preclinical or clinical development. As of 2015, TUG-770 and CNX-011-67 (Connexios Life Sciences, Karnataka, India) were in preclinical trials and JTT-851 (Japan Tobacco, Toyko, Japan), and P11187 (Piramal, Mumbai, India) were in clinical trails. </div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">[[Image:AMG-837.jpg |300 px|right|thumb|Figure 5. Structure of the potential agonist AMG-837. In clinical trials, this drug was found to increase glucose tolerance in individuals with Type 2 Diabetes.]] </ins>TAK-875 had the most promising outlooks out of any current known agonists of hGPR40, but it was discontinued. Some other agonists tested in clinical trials include AMG-837 and AM-1638. When coadministered, AMG-837 <ins style="color: red; font-weight: bold; text-decoration: none;">(Figure 5) </ins>and AM-1638 enhanced glucose tolerance, but they were found to be toxic in the human trials. Some other agonsits are currently being examined as well. One compound, LY 2881835, has undergone clinical trials, but the results are unknown. In addition to the above-mentioned compound, other orally bioavailable GPR40-specific agonists are currently in preclinical or clinical development. As of 2015, TUG-770 and CNX-011-67 (Connexios Life Sciences, Karnataka, India) were in preclinical trials and JTT-851 (Japan Tobacco, Toyko, Japan), and P11187 (Piramal, Mumbai, India) were in clinical trails. </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> </table>

Whitney Hart http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1170&diff=2587353&oldid=prev Jacob Applegarth at 15:48, 15 April 2016 2016-04-15T15:48:46Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 15:48, 15 April 2016</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 33:</td> <td colspan="2" class="diff-lineno">Line 33:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== Other Potential Inhibitors ===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== Other Potential Inhibitors ===</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>TAK-875 had the most promising outlooks out of any current known agonists of hGPR40, but it was discontinued. Some other agonists tested in clinical trials include AMG-837 and AM-1638. When coadministered, AMG-837 and AM-1638 enhanced glucose tolerance, but they were found to be toxic in the human trials. Some other agonsits are currently being examined as well. One compound, LY 2881835, has undergone clinical trials, but the results are unknown. </div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>TAK-875 had the most promising outlooks out of any current known agonists of hGPR40, but it was discontinued. Some other agonists tested in clinical trials include AMG-837 and AM-1638. When coadministered, AMG-837 and AM-1638 enhanced glucose tolerance, but they were found to be toxic in the human trials. Some other agonsits are currently being examined as well. One compound, LY 2881835, has undergone clinical trials, but the results are unknown<ins style="color: red; font-weight: bold; text-decoration: none;">. In addition to the above-mentioned compound, other orally bioavailable GPR40-specific agonists are currently in preclinical or clinical development. As of 2015, TUG-770 and CNX-011-67 (Connexios Life Sciences, Karnataka, India) were in preclinical trials and JTT-851 (Japan Tobacco, Toyko, Japan), and P11187 (Piramal, Mumbai, India) were in clinical trails</ins>. </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> </table>

Jacob Applegarth http://52.214.119.220/wiki/index.php?title=Sandbox_Reserved_1170&diff=2587351&oldid=prev Whitney Hart at 15:42, 15 April 2016 2016-04-15T15:42:18Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 15:42, 15 April 2016</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 31:</td> <td colspan="2" class="diff-lineno">Line 31:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== TAK-875 ===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>=== TAK-875 ===</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Tak-875.png |300 px|right|thumb|Figure 4. Structure of TAK-875. The carboxylate moiety (upper right) inserts into hGPR40. The Sulfonate group (upper left) remains on the outside of the protein once bound.]] One example of an hGPR40 agonist is <scene name='72/721541/Tak875/3'>TAK-875</scene>. The carboxylate moiety of the agonist enters through the auxiliary loop of hGPR40, disrupts the hydrogen bonding of the charge network, and binds with Arg183, Arg258, Tyr91, and Tyr240.<ref name="Srivastava"/> TAK-875 has shown efficacy in increasing insulin secretion and lowering blood glucose in rodent models of type 2 diabetes.<ref name="Burant"/> This drug was studied in [https://www.nlm.nih.gov/services/ctphases.html phase III clinical trials]. It significantly reduced [http://www.diabetes.co.uk/what-is-hba1c.html HbA1c] and fasting plasma glucose levels in Japanese patients with type 2 diabetes that was not controlled by diet and exercise. However, clinical trials were stopped shortly after this study because TAK-875 was suspected of causing liver damage.<ref name="Kaku">PMID:25787200</ref> </div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Tak-875.png |300 px|right|thumb|Figure 4. Structure of TAK-875. The carboxylate moiety (upper right) inserts into hGPR40. The Sulfonate group (upper left) remains on the outside of the protein once bound.]] One example of an hGPR40 agonist is <scene name='72/721541/Tak875/3'>TAK-875</scene>. The carboxylate moiety of the agonist enters through the auxiliary loop of hGPR40, disrupts the hydrogen bonding of the charge network, and binds with Arg183, Arg258, Tyr91, and Tyr240.<ref name="Srivastava"/> TAK-875 has shown efficacy in increasing insulin secretion and lowering blood glucose in rodent models of type 2 diabetes.<ref name="Burant"/> This drug was studied in [https://www.nlm.nih.gov/services/ctphases.html phase III clinical trials]. It significantly reduced [http://www.diabetes.co.uk/what-is-hba1c.html HbA1c] and fasting plasma glucose levels in Japanese patients with type 2 diabetes that was not controlled by diet and exercise. However, clinical trials were stopped shortly after this study because TAK-875 was suspected of causing liver damage.<ref name="Kaku">PMID:25787200</ref> </div></td></tr> <tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"></td></tr> <tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>=== Other Potential Inhibitors ===</div></td></tr> <tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>TAK-875 had the most promising outlooks out of any current known agonists of hGPR40, but it was discontinued. Some other agonists tested in clinical trials include AMG-837 and AM-1638. When coadministered, AMG-837 and AM-1638 enhanced glucose tolerance, but they were found to be toxic in the human trials. Some other agonsits are currently being examined as well. One compound, LY 2881835, has undergone clinical trials, but the results are unknown. </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> </table>

Whitney Hart