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Modulating Bitter Taste Receptors

Chemoreceptors are specialized sensory receptor cells that transduce a chemical substance (endogenous or exogenous) to generate a biological signal. There are many such receptor cells but the most widely recognized are taste receptors; generally categorized as ‘sweet’ or ‘bitter’.  Although we think of taste receptors as those ‘buds’ on our tongue that help us distinguish candy from cod liver oil, taste receptors are found throughout the body; typically, on mucosal lined epithelial cells including the gastrointestinal tract, respiratory tract, and genitourinary tract, but can also be found in certain organs such as the heart, liver, ovaries and testes.  One can think of taste receptors as medicine's ‘first’ therapeutic targets. As an example, quinine is a bitter compound that engages certain bitter taste receptors and is the only adequate treatment for malaria.  Its use, as a medicinal product, dates to the mid 1600’s. 

Amaro is currently focused on the modulation of bitter taste receptors (TAS2R) for which 25 have been identified in humans (e.g., TAS2R1, TAS2R14, etc.).  The potential implications of modulating TAS2R are tremendous in that a single receptor likely has different biological function(s) depending on the tissue or organ in which it is expressed.  This creates a large combinatoric biology space in which to identify possible therapeutic indications.  We think of that space in the context of the combination of a systemic effect (i.e., those effects initiated by receptors in the GI tract such as increases in GLP-1) with tissue-specific effects (i.e., a decrease in adiponectin in adipose tissue combined with a decrease in androgen expression in ovaries) driven by modulation of a single TAS2R (i.e., TAS2R1).  We believe the opportunity provided by the combinatorics of TAS2R modulation provides multiple “shots on goal” in high unmet immune-metabolic conditions such as PCOS, obesity, diabetes and NASH.

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