Activating bitter taste receptors may one day treat asthma and COPD

Surprisingly, there are bitter taste receptors in the airways and may have potential to treat asthma or chronic obstructive pulmonary disease (COPD).

A research published in Journal of Medicinal Chemistry of the American Chemical Society (ACS) have engineered a potent, selective compound that may lead the way in treating asthma and chronic obstructive pulmonary disease (COPD) in surprising ways. Of the 25 different types of bitter taste receptors, the TAS2R14 subtype is one of the most widely distributed in tissues outside the mouth, being found in the respiratory tract.

Scientists do not know the structure of the receptor and have not identified the specific compound or “ligand” in the body that activates it. However, some synthetic compounds, such as the nonsteroidal anti-inflammatory drug (NSAID) flufenamic acid, are known to bind to and activate TAS2R14. But these compounds are not very potent and do not have similar structural characteristics.

ACS researchers used flufenamic acid as a starting point to design and synthesize analogues with improved properties. Building on their earlier findings that certain types of structures improved power, the researchers made variations that they tested in a cellular assay that measures receptor activation.

Replacing a phenyl ring with a 2-aminopyrimidine and a carboxylic acid group with a tetrazole was the strategy that worked. One of the new ligands was six times more potent than flufenamic acid, meaning that less compound was needed to produce a similar response. This ligand was also highly selective for TAS2R14 compared to non-bitter taste receptors, which could minimize side effects. According to the researchers, the new compounds will help to elucidate the structure, mechanism and physiological function of bitter taste receptors and will guide the development of drugs targeting them.


Discovery of 2-Aminopyrimidines as potent agonists for the TAS2R14 bitter taste receptor

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