Researchers at Cincinnati Children’s have discovered a compound that blocks the inflammatory activity of the transcription factor FOXM1 in asthma.
The finding was reported April 18, 2017, in Science Signaling.
Vladimir Kalinichenko, MD, PhD
The compound, RCM-1, prevents excess inflammation and mucous in mouse models and human respiratory cells.
Transcription factors, tiny proteins that switch genes on and off in cell nuclei, have long been considered unreachable targets for drug treatments.
“Traditional targets for drugs are receptors on cell surfaces, which are easy to reach. Transcription factors are inside cell nuclei and difficult to reach,” says Vladimir Kalinichenko, MD, PhD, the study’s lead investigator and a member of the Division of Pulmonary Biology. “RCM-1 keeps FOXM1 from entering the cell nucleus by activating cell machinery called proteasomes that degrade the transcription factor. This was very efficient at reducing lung inflammation and production of mucous-generating goblet cells in our tests.”
Kalinichenko’s team believes the discovery could lead to clinical trials for asthma, cystic fibrosis and chronic obstructive pulmonary disease.