Unknown

Dataset Information

0

Structure-Activity Relationship and Biological Investigation of SR18292 (16), a Suppressor of Glucagon-Induced Glucose Production.


ABSTRACT: Despite a myriad of available pharmacotherapies for the treatment of type 2 diabetes (T2D), challenges still exist in achieving glycemic control. Several novel glucose-lowering strategies are currently under clinical investigation, highlighting the need for more robust treatments. Previously, we have shown that suppressing peroxisome proliferator-activated receptor gamma coactivator 1-alpha activity with a small molecule (SR18292, 16) can reduce glucose release from hepatocytes and ameliorate hyperglycemia in diabetic mouse models. Despite structural similarities in 16 to known β-blockers, detailed structure-activity relationship studies described herein have led to the identification of analogues lacking β-adrenergic activity that still maintain the ability to suppress glucagon-induced glucose release from hepatocytes and ameliorate hyperglycemia in diabetic mouse models. Hence, these compounds exert their biological effects in a mechanism that does not include adrenergic signaling. These probe molecules may lead to a new therapeutic approach to treat T2D either as a single agent or in combination therapy.

SUBMITTER: Lin H 

PROVIDER: S-EPMC7869975 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC5554950 | biostudies-literature
| S-EPMC10845918 | biostudies-literature
| S-EPMC2940466 | biostudies-literature
| S-EPMC5428006 | biostudies-literature
| S-EPMC6272548 | biostudies-literature
| S-EPMC3953686 | biostudies-literature
| S-EPMC5695911 | biostudies-literature
| S-EPMC1134640 | biostudies-other
2017-10-20 | PXD005677 | Pride
| S-EPMC7496872 | biostudies-literature