Novel compound may help develop diabetes drugs

Date:
January 27, 2021
Source:
Ohio State University Wexner Medical Center
Summary:
A study has identified a new compound that might serve as a basis
for developing a new class of drugs for diabetes.



FULL STORY ========================================================================== Research led by The Ohio State University Wexner Medical Center and
College of Medicine identified a new compound that might serve as a
basis for developing a new class of drugs for diabetes.


========================================================================== Study findings are published online in the journal Nature Chemical
Biology.

The adenosine monophosphate-activated protein kinase (Ampk) is a crucial
enzyme involved in sensing the body's energy stores in cells. Impaired
energy metabolism is seen in obesity, which is a risk factor for
diabetes. Some medications used to treat diabetes, such as metformin,
work by increasing 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," said Dr. Rama
K. Mallampalli, senior author and chair of the department of internal
medicine at Ohio State.

Mallampalli began this research at The University of Pittsburgh before
joining Ohio State, and continued collaborating with researchers there
to complete the study.

"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," Mallampalli said. "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." Mallampalli reports a financial interest in the
compound licensed to the University of Pittsburgh.

This work is support by the American Heart Association; U.S. Department
of Health & Human Services; U.S. National Institute of Diabetes and
Digestive and Kidney Diseases; National Institutes of Health and the
National Heart Lung and Blood Institute; United States Department of
Veterans Affairs and Veterans Health Administration.


========================================================================== Story Source: Materials provided by Ohio_State_University_Wexner_Medical_Center. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Yuan Liu, Michael J. Jurczak, Travis B. Lear, Bo Lin, Mads
B. Larsen,
Jason R. Kennerdell, Yanwen Chen, Brydie R. Huckestein, Matthew K.

Nguyen, Ferhan Tuncer, Yu Jiang, Satdarshan P. Monga, Christopher P.

O'Donnell, Toren Finkel, Bill B. Chen, Rama K. Mallampalli. A
Fbxo48 inhibitor prevents pAMPKa degradation and ameliorates
insulin resistance.

Nature Chemical Biology, 2021; DOI: 10.1038/s41589-020-00723-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/01/210127085215.htm

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