RT Journal Article
SR Electronic
T1 Inhibition of Bitter Taste from Oral Tenofovir Alafenamide
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 319
OP 327
DO 10.1124/molpharm.120.000071
VO 99
IS 5
A1 Erik Schwiebert
A1 Yi Wang
A1 Ranhui Xi
A1 Katarzyna Choma
A1 John Streiff
A1 Linda J. Flammer
A1 Natasha Rivers
A1 Mehmet Hakan Ozdener
A1 Robert F. Margolskee
A1 Carol M. Christensen
A1 Nancy E. Rawson
A1 Peihua Jiang
A1 Paul A. S. Breslin
YR 2021
UL http://molpharm.aspetjournals.org/content/99/5/319.abstract
AB Children have difficulty swallowing capsules. Yet, when presented with liquid formulations, children 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 culture as a screening platform. Specifically, TAS2R39 and TAS2R1 are the main type 2 taste receptors responding to TAF observed via heterologously expressing specific TAS2R receptors into HEK293 cells. In this assay, 6-methylflavone blocked the responses of TAS2R39 to TAF. In human sensory testing, 8 of 16 subjects showed reduction in perceived bitterness of TAF after pretreating (or “prerinsing”) 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 tenofovir alafenamide may increase the compliance in treating children with human immunodeficiency virus infections.