DAEJEON — KAIST announced on July 2, 2026, that a research team led by Professor Mi Hee Lim of the Department of Chemistry developed a prodrug designed to activate selectively in the brains of Alzheimer's disease patients. The prodrugs, named BE-1 and BE-2, are intended to become active when encountering hydrogen peroxide, which is increased in the brains of individuals with Alzheimer's disease.

When BE-1 and BE-2 encounter hydrogen peroxide in a dementia-affected brain, they convert into active therapeutic compounds known as AP-1 and AP-2. The activated drug reduces reactive oxygen species, including hydrogen peroxide, and prevents amyloid beta peptides from aggregating into clumps. The research team confirmed that the activated drug alters the morphology of amyloid beta aggregates and suppresses their growth into larger aggregates.

In Alzheimer's disease mouse models, the drug crossed the blood-brain barrier and converted into the therapeutic compound inside the diseased brain. Long-term drug administration in mice resulted in reduced oxidative stress in the hippocampus and decreased amyloid beta accumulation in the brain. Behavioral experiments, which assessed the ability to recognize new objects and navigate mazes in mice, showed improvement in cognitive function.

Professor Lim stated, "We expect this strategy, which activates drugs in diseased tissue, to become a new platform for treating complex diseases such as Alzheimer's disease more safely and effectively." The study's co-first authors were Jimin Lee and Eunseo Hong, Ph.D. candidates in KAIST's Department of Chemistry. The research team also included Professor Mingeun Kim of Chonnam National University, Dr. Chul-Ho Lee and Dr. Kyoung-Shim Kim of the Korea Research Institute of Bioscience and Biotechnology, and Dr. Young-Ho Lee of the Korea Basic Science Institute. The study was published online in the journal Small on May 31, 2026.