Broad Spectrum Bitter Taste Antagonists Discovery

Principal Investigators for Small Business: DiscoveryBioMed, Inc. (DBM) and Monell Chemical Senses Center
Project Summary Abstract
Bitter taste in foods and medicines presents a barrier to overcoming global public health challenges: food
insecurity, poor nutritional health, and poor compliance with medication use, particularly among children and
the elderly. Sugar and salt, the mainstays to address these challenges, further erode nutritional health, and
current alternatives have adverse taste attributes of their own. We propose to develop a reliable, human taste-
cell screening platform to find bitter blockers of commercial interest to the food, flavor, and pharmaceutical
industries, with the ultimate commercial aim to improve the taste and acceptance of nutritious and sustainable
foods and medicines. This Phase 2 STTR proposal evolves from a successful Phase 1 STTR funded program
to establish primary and immortal human taste-bud-derived epithelial cell cultures and lines (i.e., hTBEC
platforms) from donors with bitter-sensitive genotypes and (b) to design, optimize, and implement hTBEC-
based bioassays of bitter taste receptor function and other key end points to produce readout data for medium-
throughput screening (MTS). Preliminary data is presented in support of the proposed MTS campaign. This
Phase 2 STTR proposal seeks to deepen MTS with bitter-responsive hTBEC platforms as the key ingredient.
Milestone 1 of the proposal will be underpinned by three specific experimental aims to complete MTS and
perform cheminformatics to realize multiple chemical classes that are bitter taste antagonists. Genomic and
qRT-PCR analysis of key TAS2R bitter receptors will be performed continually in parallel to insure stability and
robustness of the bitter-responsive hTBEC platforms. Milestone 2 of the proposal will identify ‘broad spectrum’
bitter taste antagonists with future marketplace utility and will be underpinned by two specific experimental
aims involving secondary validation of bitter taste antagonists in receptor-specific assays, ‘bitterome’
genomics, and human taste behavior. Industry collaborators will test our best candidate bitter taste antagonists
independently for rigor and reproducibility against their bitter drugs (e.g., active product ingredients or APIs).
Milestone 3 of the proposal will focus on characterizing deeply and selecting the best bitter-responsive hTBEC
platforms and bioassays for clients and to optimize and partner bitter taste antagonists with industry to realize
new formulations for bitter-tasting drugs and bitter-tasting foods and beverages. This collaboration between
DiscoveryBioMed, Inc. and Monell Chemical Senses Center brings together expertise in (a) culture of human
taste cells, (b) the creation of immortalized cell lines, (c) MTS, (d) genetics and (e) human sensory analysis.
The guiding hypothesis is that hTBEC-platform-based bioassays will provide a more relevant robust way to
discover novel ‘bitter blockers’, given the imperfect current methods of overexpressing known taste receptors
in heterologous cells. The discovery of bitter taste receptor antagonists that alone or blended together block
bitter taste can improve healthy eating by reducing reliance on salt and sugar and can improve compliance by
patients taking medicines. Thus, we are confident that new bitter blockers will improve human health.
PHS 398/2590 (Rev. 09/04, re-issued 4/2006) Page Continuation Format PagePrincipal Investigators for Small Business: DiscoveryBioMed, Inc. (DBM) and Monell Chemical Senses Center
Public Health Relevance Statement
Bitter taste in foods and medicines stymies efforts to improve nutritional health, alleviate food insecurity and
accounts in part for poor compliance by patients, who fail to take medication as prescribed. Sugar and salt, the
mainstays to address these challenges, further erode health, and current but imperfect alternatives to these
bitter-masking compounds have adverse taste attributes of their own. We propose to implement a reliable,
human taste-cell screening platform to find acceptable bitter blockers of commercial interest to the food, flavor,
and pharmaceutical industries, with the ultimate goal to improve the taste and acceptance of nutritious and
sustainable foods and medicines.
PHS 398/2590 (Rev. 09/04, re-issued 4/2006) Page Continuation Format Page