Broad Spectrum Bitter Taste Antagonists Discovery

广谱苦味拮抗剂的发现

• 批准号: 10405281
• 负责人: DANIELLE Renee REED
• 金额: $ 2.09万
• 依托单位: DISCOVERYBIOMED, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10405281
• 关键词: Address; Affect; Applied Research; Behavior; Beverages; Biological Assay; Businesses; Cell Culture Techniques; Cell Line; Cells; Chemicals; Child; Client; Collaborations; Data; Drug Industry; Elderly; Epithelial Cells; Food; Food Industry; Formulation; Foundations; Funding; Fungiform Papilla; Future; Genetic; Genetic Variation; Genomics; Genotype; Goals; Health; Healthy Eating; Human; Individual; Industry; Industry Collaboration; Institutes; Intellectual Property; International; Joints; Lead; Ligands; Masks; Medicine; Messenger RNA; Methods; Nutritional; Organic Chemicals; Output; Palate; Personal Satisfaction; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Philadelphia; Physiological; Phytochemical; Primary Cell Cultures; Principal Investigator; Proteins; Public Health; Quantitative Reverse Transcriptase PCR; Recommendation; Reporter; Reproducibility; Research; Research Contracts; Research Personnel; Science; Sensory; Signal Transduction; Small Business Technology Transfer Research; Sodium Chloride; Structure-Activity Relationship; Target Populations; Taste Bud Cell; Taste Buds; Taste Perception; Technology; Testing; Tongue; Validation; base; behavior test; cell immortalization; cheminformatics; clinically relevant; compliance behavior; cytotoxicity; design; dietary; drug discovery; ethnic diversity; experimental study; food challenge; food flavor; food insecurity; genetic variant; human subject; improved; innovation; interest; novel; overexpression; programs; public health relevance; receptor; receptor function; reduced food intake; response; salt intake; screening; small molecule; sugar; transcriptome sequencing; validation studies

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 Page

小型企业的主要研究者：DiscoveryBioMed， Inc. （DBM）和Monell化学感官中心

项目成果

Inhibition of Bitter Taste from Oral Tenofovir Alafenamide.

口服替诺福韦艾拉酚胺对苦味的抑制。

• DOI: 10.1124/molpharm.120.000071
• 发表时间: 2021
• 期刊: Molecular pharmacology
• 影响因子: 3.6
• 作者: Schwiebert,Erik;Wang,Yi;Xi,Ranhui;Choma,Katarzyna;Streiff,John;Flammer,LindaJ;Rivers,Natasha;Ozdener,MehmetHakan;Margolskee,RobertF;Christensen,CarolM;Rawson,NancyE;Jiang,Peihua;Breslin,PaulAS
• 通讯作者: Breslin,PaulAS