Key points:
- Researchers developed new compounds that can mimic exercise’s ability to enhance muscle metabolism, growth and performance in rodent cells.
- The compounds bind, activate, and trigger strong responses of three estrogen-related receptors—ERRα, ERRβ and ERRγ—that regulate physiological processes in muscles.
- These types of compounds have the potential to offset muscle atrophy and weakness associated with aging, cancer, and certain genetic conditions.
Researchers have identified new compounds that are capable of mimicking the physical boost of working out. Their discovery, which was presented at the spring meeting of the American Chemical Society, could uncover a new way to treat muscle atrophy and other medical conditions.
The team wanted to develop a compound that would recapitulate exercise’s ability to enhance muscle cell’s metabolism and growth as well as its influence on muscle performance. This type of drug could offset the muscle atrophy and weakness that is associated with aging, cancer, and certain genetic conditions.
To identify this compound, researchers examined the structure and binding of estrogen-related receptors (ERRs) as these receptors regulate exercise-induced stress adaptation and physiological processes in muscles. After almost a decade of work, they developed SLU-PP-332 which activates all three ERR forms—ERRα, ERRβ and ERRγ. In experiments with mice, SLU-PP-332 increased a fatigue-resistant type of muscle fiber while improving endurance when animals ran on a rodent treadmill.
The team then designed molecules that could strengthen the interactions with receptors and trigger a stronger response than SLU-PP-332 alone. They optimized their compounds for desirable characteristics such as stability and low toxicity.
Next, they compared the potency of their new compounds with that of SLU-PP-332 by examining RNA from about 15,000 genes in rat heart muscle cells. Importantly, the new compounds provided a greater increase in the presence of RNA, meaning they more potently simulate the effects of exercise.
“We cannot replace exercise; exercise is important on all levels,” said project principal investigator Bahaa Elgendy of Washington University. “If I can exercise, I should go ahead and get the physical activity. But there are so many cases in which a substitute is needed.”