Syracuse Sun

Over the past year and a half, Robert Doyle, a medicinal chemist at Syracuse University, has introduced two peptide compound discoveries at conferences of the American Chemical Society and The Obesity Society. These compounds reportedly reduce body weight and normalize blood glucose levels without the side effects commonly associated with current GLP-1-based anti-obesity drugs.

Doyle, along with his collaborators, is refining these compounds—GEP44 and KCEM1—through lab-animal testing and patent filings. They are exploring market placement for these drugs, which they believe could significantly advance obesity and diabetes treatment globally. Another promising compound discovered by the team shows potential in treating opioid addiction.

Doyle holds dual positions as a professor of pharmacology and medicine at SUNY Upstate Medical University. He collaborates with Matthew Hayes from the University of Pennsylvania Perelman School of Medicine and Christian Roth from Seattle Children’s Research Institute on this research.

GEP44 targets multiple receptors in the brain, pancreas, and liver simultaneously. “It’s sort of a reboot of the body’s computer,” Doyle says. However, it requires daily injections—a challenge for many patients—so researchers are working on a long-acting version.

The second compound, KCEM1, aims to treat hypothalamic obesity in children. Testing is ongoing in collaboration with German researchers who identified the causative gene.

Doyle and Hayes have also developed another compound called DG260 that targets different mechanisms to promote weight loss without adverse side effects while offering additional health benefits.

An unexpected finding was GEP44's ability to reduce cravings in opioid-addicted lab animals. This discovery may lead to new therapies for reducing human drug cravings. Heath Schmidt from the University of Pennsylvania is collaborating on this aspect.

The compounds are produced at Syracuse University's Center for Science and Technology using advanced equipment funded partly by a $3 million grant from the U.S. Department of Defense Congressionally Directed Medical Research Programs.

“We couldn’t have gotten anywhere near where we are now without that initial DoD grant,” Doyle states.

The research provides significant opportunities for students at various academic levels through involvement in cutting-edge projects supported by additional National Institutes of Health grants totaling over $6 million.

Reflecting on their eight-year journey focused on safety and tolerability, Doyle acknowledges growing awareness about existing drug side effects: “Now everyone knows that these side effects are a problem.” He anticipates an increase in developing effective weight-loss medicines without current drawbacks within five to ten years: “We’re trying to drive that forward from Syracuse University.”