Columbus, Ohio – Research led by Ohio State University’s Wexner Medical Center and College of Medicine has identified a new compound that may serve as the basis for developing a new class of drugs for diabetes.
The study results are published online in the journal Biology of Chemical Nature.
Monophosphate-activated protein kinase (Ampk) is an important enzyme involved in sensing the body’s energy stores in cells. Impaired energy metabolism is seen in obesity, which is a risk factor for developing diabetes. Some drugs used to treat diabetes, such as metformin, work by increasing AMPC activity.
“In our study we discovered a protein involved in removing Ampk from cells called Fbxo48. We designed and tested a compound called BC1618, which blocks Fbxo48 and was much more powerful than metformin in increasing Ampk function.” Said Dr. Rama K. Malambali, senior author and chief of internal medicine in Ohio BC1618: “BC1618 improved responses to insulin, a measure of the effectiveness of diabetes medications, in obese mice.”
Malambali began this research at the University of Pittsburgh before joining Ohio, and has continued to collaborate with researchers there to complete studies.
This study builds on our previous research to understand how important proteins in the body are removed or degraded. The research team had previously designed and produced a family of anti-inflammatory drugs that has been approved by the FDA and is preparing to enter phase 1 studies. “Using this new compound as a backbone, our team including Dr. Bill Chen and Dr. Yuan Liu in Pittsburgh will create other compounds that are more effective and safer in animal models and then test them in animal models with diabetes. Ultimately, we aim to get FDA approval.” (FDA) to conduct human testing. ”
Malambali reports that there is a financial interest in the University of Pittsburgh Licensed Complex.
This work is supported by the American Heart Association. US Department of Health and Human Services; US National Institute of Diabetes and Digestive and Kidney Diseases; The National Institutes of Health and the National Heart, Lung, and Blood Institute; United States Department of Veterans Affairs and Veterans Health Administration.