Researchers identify a new compound for creating a new class of diabetes drugs

A new study headed by the Ohio State University Wexner Medical Center and the College of Medicine has found a new compound that could form the base for creating a new class of diabetes drugs.

Researchers identify a new compound for creating a new class of diabetes drugs
Dr Rama K. Mallampalli is professor and chair of the Department of Internal Medicine at The Ohio State University Wexner Medical Center and The Ohio State University College of Medicine. Image Credit: The Ohio State University Wexner Medical Center.

The results of the research have been published online in the Nature Chemical Biology journal. Adenosine monophosphate-activated protein kinase (Ampk) is a key enzyme involved in the identification of energy reserves of the body in cells.

Obesity, a risk factor for diabetes, presents an impaired energy metabolism. Certain medicines used for diabetes treatment, like metformin, work by elevating the activity of Ampk.

In our study, we discovered a protein that is involved in removing Ampk from cells called Fbxo48. We designed and tested a compound termed, BC1618, that blocks Fbxo48 and was much more potent than metformin in increasing Ampk function. BC1618 improved responses to insulin, a measure of effectiveness for diabetes medicines, in obese mice.”

Dr Rama K. Mallampalli, Study Senior Author and Chair, Department of Internal Medicine, The Ohio State University Wexner Medical Center

Mallampalli started this study at the University of Pittsburgh before joining Ohio State and proceeded to collaborate with researchers there to complete the research.

This study builds on our prior research to understand how critical proteins in the body are removed or degraded. The research team had previously designed and produced a family of anti-inflammatory drugs that are FDA approved and are poised to enter Phase 1 studies.”

Dr Rama K. Mallampalli, Study Senior Author and Chair, Department of Internal Medicine, The Ohio State University Wexner Medical Center

Using this new compound as a backbone, our team including Dr. Bill Chen and Dr. Yuan Liu at Pittsburgh will make other compounds that are more potent and safe in animal models and then test them in diabetes animal models. Eventually, we aim to obtain FDA approval for human testing,” added Mallampalli.

Source:
Journal reference:

Liu, Y., et al. (2021) A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistance. Nature Chemical Biology. doi.org/10.1038/s41589-020-00723-0.

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