Scientists at NYU Langone Health have discovered a new drug compound that may help treat some of the most serious problems caused by diabetes.
In studies with mice, this compound reduced inflammation, limited cell damage, and helped organs like the heart and kidneys recover better. It even sped up wound healing. The drug, called RAGE406R, works by stopping two harmful proteins—RAGE and DIAPH1—from interacting.
This discovery, which was recently highlighted on the cover of the journal Cell Chemical Biology, focuses on a different approach from most diabetes medications.
Instead of lowering blood sugar, RAGE406R works inside the body’s cells to stop damage before it happens. If further tests in humans are successful, this treatment could offer hope for people with both Type 1 and Type 2 diabetes.
Diabetes can lead to long-term complications, including kidney failure, heart disease, and slow healing of cuts and wounds. These problems often happen because of molecules called AGEs, or advanced glycation end products.
These molecules form when sugars stick to proteins or fats in the body—a process that happens more often in people with diabetes. When AGEs build up, they bind to a protein called RAGE, which triggers damage and inflammation.
One key part of this process is the protein DIAPH1, which connects to the inner part of RAGE and helps form parts of the cell’s inner structure. This interaction makes the effects of AGEs worse. The researchers found that the new compound RAGE406R blocks DIAPH1 from binding to RAGE, which reduces the harmful activity inside the cell.
In lab experiments and tests on mice, the compound worked well to reduce symptoms linked to diabetes. The researchers applied it to the skin of mice with Type 2 diabetes and found that it helped wounds heal faster. This is important because people with diabetes often suffer from wounds that don’t close properly and can become infected.
The drug also helped calm the immune system. In people with diabetes, inflammation often happens where it shouldn’t or lasts longer than it should.
RAGE406R lowered the levels of a molecule called CCL2, which is a signal that tells immune cells to gather at a site of injury. By reducing CCL2, the drug helped prevent unnecessary inflammation and allowed tissues to heal properly.
This work builds on earlier research by the same team. Their first compound, RAGE229, showed promise but failed safety tests because of concerns it might damage DNA. The new version, RAGE406R, was redesigned to avoid that risk while keeping its helpful effects.
Researchers believe this new compound opens up a new path for treating diabetes. It could also help scientists find better ways to measure how well treatments are working. If human trials confirm these results, RAGE406R could one day offer a safer and more effective way to manage complications of diabetes without targeting blood sugar levels directly.
This research is still in the early stages, but it represents an exciting step toward better treatments for millions of people living with diabetes.
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