Sandbox Reserved 1170: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Whitney Hart (talk | contribs) No edit summary |
Whitney Hart (talk | contribs) No edit summary |
||
| Line 31: | Line 31: | ||
=== TAK-875 === | === TAK-875 === | ||
[[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> | [[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> | ||
=== Other Potential Inhibitors === | |||
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. | |||
