TY - JOUR T1 - <strong>Inhibition of bitter taste from oral Tenofovir Alafenamide (TAF)</strong> JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/molpharm.120.000071 SP - MOLPHARM-AR-2020-000071 AU - Erik Schwiebert AU - Yi Wang AU - Ranhui Xi AU - Katarzyna Choma AU - John Streiff AU - Linda J. Flammer AU - Natasha Rivers AU - Mehmet Hakan Ozdener AU - Robert F. Margolskee AU - Carol M. Christensen AU - Nancy E. Rawson AU - Peihua Jiang AU - Paul A.S. Breslin Y1 - 2021/01/01 UR - http://molpharm.aspetjournals.org/content/early/2021/04/06/molpharm.120.000071.abstract N2 - Children have difficulty swallowing capsules. Yet, when presented with liquid formulations often reject oral medications due to their intense bitterness. Presently, effective strategies to identify methods, reagents, and tools to block bitterness remain elusive. For a specific bitter-tasting drug, identification of the responsible bitter receptors and discovery of antagonists for those receptors can provide a method to block perceived bitterness. We have identified a compound (6-methylflavone) that can block responses to an intensely bitter-tasting anti-Human Immunodeficiency Virus (HIV) drug, tenofovir alafenamide (TAF), using a primary human taste bud epithelial cell (hTBEC) culture as a screening platform. Specifically, TAS2R39 and TAS2R1 are the main T2R receptors responding to TAF observed via heterologously expressing specific TAS2R receptors into HEK-293 cells. In this assay, 6-methylflavone blocked the responses of TAS2R39 to TAF. In human sensory testing, eight of sixteen subjects showed reduction in perceived bitterness of TAF after pre-treating (or 'pre-rinsing') with 6-methylflavone and mixing 6-methylflavone with TAF. Bitterness was completely and reliably blocked in two of these subjects. These data demonstrate that a combined approach of human taste cell culture-based screening, receptor-specific assays, and human psychophysical testing can successfully discover molecules for blocking perceived bitterness of pharmaceuticals, such as the HIV therapeutic TAF. Our hope is to use bitter taste blockers to increase medical compliance with these vital medicines. Significance Statement Identification of a small molecule that inhibits bitter taste from TAF may increase the compliance in treating children with HIV infections. ER -