It targets allergy sensitive lungs by destroying a tiny protein previously considered untouchable.
Tests on mice and human tissue showed the compound, called RMC-1, removed the chemical, known as a 'transcription factor', from the nucleus of cells.
Called FOXM1, the protein triggers inflammation and mucous in diseases like asthma and COPD (chronic obstructive pulmonary disorder).
It also plays a key role in lung cancer.
Transcription factors control the activity of genes by switching them on and off.
They are so embedded they were thought to be out of the reach of drugs attempting to treat medical conditions.
Pulmonary biologist Dr Vladimir Kalinichenko, of Cincinnati Children's Hospital, said: "Traditional targets for drugs are receptors on cell surfaces, which are easy to reach.
"Transcription factors are inside cell nuclei and difficult to reach.
"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
"This was very efficient at reducing lung inflammation and production of mucous generating goblet cells in our tests."
The breakthrough published in Science Signaling offers hope of the first new asthma drug in twenty years.
Dr Kalinichenko said the drug blocked the transcription factor FOXM1, preventing a chain of inflammatory processes fuelled in asthmatic lungs.
The treatment stopped over production of mucous cells, or goblet cells, in the lungs of asthmatic mice and in human lung cells grown in the laboratory.
This could open the door to using for cystic fibrosis which causes the lungs to flood with mucous.
The researchers are optimistic the discovery will lead to clinical trials for asthma, cystic fibrosis and COPD - all severe diseases caused by inflammation and a build up of mucous in the lungs.
Asthma can be triggered by the weather, your emotions and even sex. Knowing what your triggers are, will help you cope and deal with your asthma more effectively.
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Dr Kalinichenko said the study was driven by the need to develop more effective treatments.
Current clinical management for asthma focuses on reducing lung and airway inflammation triggered by allergens, such as house dust mites and mould.
Drugs that directly affect genes that trigger inflammation and mucous-producing goblet cells would potentially be more efficient at slowing or even curing disease.
Dr Kalinichenko and colleagues identified RCM-1 by screening 50,000 small compounds stored on a computer at the university's Genome Research Centre.
They searched specifically for those that would target FOXM1 and inhibit its activation of inflammatory molecules that drive over production of mucous.
They then injected RMC-1 into cultured human lung cells and mice engineered to develop asthma by being sensitised to house dust mites or being treated with an inflammatory molecule called IL-13 which fuels mucous production in diseases.
Under the microscope, the researchers could see how RMC-1 prevented FOXM1 from entering the nucleus of human lung cells and the respiratory airways of the mice.
It also reduced sensitivity to asthma triggering allergens in the mice - boosting lung function and decreasing inflammation.
The compound also prevented IL-13 from increasing mucous cells in mice given the molecule through the nose.
Dr Kalinichenko said his team now need to test RCM-1 in more sophisticated animal models of respiratory diseases before human trials can begin.
This will help address issues including dosage, toxicity and how best to deliver the compound into patients.
They also want to refine the chemical structure of RCM-1 to make it more efficient and improve the method of delivery.
This includes seeing if it can be packaged into nano particles for intravenous injection.
The researchers have applied for a patent on RCM-1, working through the Cincinnati Children's Centre for Technology Commercialisation.
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