Interestingly, bitter taste receptors are not just found in the mouth but also in other parts of the body, such as the airways. When activated, these receptors can open lung passages, making them a possible target for treating asthma or chronic obstructive pulmonary disease (COPD). In a recent study
, researchers have developed a powerful and selective compound that could pave the way for potential therapies.
Among the 25 different types of bitter taste receptors, the TAS2R14 subtype is one of the most widely distributed in tissues outside the mouth. Scientists are uncertain about the structure of the receptor, and they haven’t identified the particular compound or “ligand” in the body that activates it. However, a few synthetic compounds, such as the nonsteroidal anti-inflammatory drug flufenamicBut these compounds aren’t very potent, and they don’t have similar structural features.
Building on their earlier findings that certain types of structures enhanced potency, the researchers made several new variations. They tested these compounds in a cell-based assay that measures receptor activation. This approach revealed that replacing a phenyl ring with a 2-aminopyrimidine and substituting a tetrazole for a carboxylic acid group was a promising strategy.
This ligand was also highly selective for TAS2R14 compared to non-bitter taste receptors, which could potentially minimize side effects. The new compounds will help shed light on the structure, mechanism, and physiological function of bitter taste receptors and guide the development of drug candidates to target them, the researchers say.
Reference: “Discovery of 2-Aminopyrimidines as Potent Agonists for the Bitter Taste Receptor TAS2R14” by Lukas Waterloo, Harald Hübner, Fabrizio Fierro, Tara Pfeiffer, Regine Brox, Stefan Löber, Dorothee Weikert, Masha Y. Niv and Peter Gmeiner, 27 February 2023,
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