The drug could help patients who are unable to work out.

Exercise is good to keep organisms healthy but some people are unable to attend work-out sessions. This is one of the reasons researchers at the Washington University School of Medicine in St. Louis have developed compounds that, in tests on rodent cells, seem to imitate the effects of exercise.

While presenting their findings at the American Chemical Society’s (ACS) Spring 2024 meeting, the scientists said their drug could help treat muscle loss and other health problems like heart failure and brain diseases.

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“We can't fully replace exercise; it's still very important. But in some cases, people need an alternative,” Bahaa Elgendy, the lead researcher, was quoted as saying in a press release of the Washington University School of Medicine.

Elgendy and his team are trying to recreate the benefits of exercise, which include improved muscle growth and metabolism. A drug that could mimic exercise might help prevent muscle loss in people who can't work out due to aging, illness, or other reasons.

The benefits of exercise start with the activation of proteins called estrogen-related receptors (ERRs), which come in three types: ERRα, ERRβ, and ERRγ. After 10 years of research, Elgendy’s team developed a compound called SLU-PP-332 that activates all three types, especially the difficult-to-target ERRα. In tests on mice, this compound improved endurance and muscle strength.

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The researchers studied the ERR structure and how it connects with molecules that activate it. They then designed new compounds that were even more effective than SLU-PP-332. These new compounds not only triggered a stronger response but were also more stable and less toxic.

When the researchers compared the effects of SLU-PP-332 and the new compounds on rat heart muscle cells, they found that the new compounds had a stronger effect. This suggests that they could better mimic exercise.

Early research shows that targeting ERRs could help treat conditions like obesity, heart failure, and age-related kidney decline. The new compounds may have similar benefits. There's also evidence that ERRs could help protect the brain in diseases like Alzheimer’s. Some of the new compounds were developed to reach the brain, unlike SLU-PP-332, which cannot.

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Elgendy and his team hope to test these new compounds in animal models through Pelagos Pharmaceuticals, a company they co-founded. They are also exploring whether these compounds could be used to treat brain diseases. Their research is supported by the National Institutes of Health.

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