SBIR-STTR Award

Natural products are rich sources for potential drugs. To accelerate drug discovery from natural products, it is imperative to identify their molecular targets, and mechanistically elucidate their bioavailability, toxicity, and therapeutic effects. However, there remain several challenges in the field. Among them, there is currently no technical platform that could perform mechanistic studies from the 'hits' to 'leads' using the small volumes of samples that are typically encountered in quantitative high-throughput screening (qHTS). In response to RFA- AT-14-001, Newomics Inc. proposes to develop a multi-omics platform for high-throughput and high-content bioassays of natural products. The core technology will be based on Newomics' breakthrough silicon- microfluidic-chip, the multinozzle emitter array chip (MEA chip-2012 R&D100 award), which enables liquid chromatography-nanoelectrospray ionization mass spectrometry (LC-nanoESI/MS)-based, highly sensitive, highly specific, high-throughput, and multiplex measurements of multiclass analytes (peptides, proteins, and metabolites) at the Omics level, from small volumes of samples. In this project, we will incorporate multiple Omics capabilities, including top-down proteomics, bottom-up proteomics, and metabolomics, on a single MEA chip, in a high-throughput and multiplex format. We will demonstrate proof-of-principle applications of our multi- omics platform in the Phase I. InAim 1, we will develop the ESI-MS assays to screen the interactions between purified human serum albumin (HSA), the most abundant protein and the key carrier of endogenous and exogenous substances in the plasma, and a selected number of natural products. In Aim 2, we will develop the Omics-based assays for probing interactions between HSA in whole blood and libraries of natural products with different complexity. Once developed, Newomics' MEA chip may become a universal platform for high- throughput identification of molecular targets of natural products in the blood or other tissues, and lay a new foundation for drug discovery and development.

Thesaurus Terms:
Address;Adduct;Artemisinine;Artemisinins;Assay Development;Award;Base;Binding (Molecular Function);Binding Sites;Biochemistry;Bioinformatics;Biological Assay;Biological Availability;Biological Factors;Biomedical Research;Biophysics;Blood;Blood Product;Cancer Stem Cell;Chemicals;Complement 4b;Complex;Cost;Crude Extracts;Development;Drug Development;Drug Discovery;Experience;Fluorescence;Foundations;High Throughput Screening;Human;Incubated;Infusion Procedures;Innovation;Instrument;Ionization;Label;Libraries;Liquid Chromatography;Malaria;Malignant Neoplasms;Mass Spectrum Analysis;Measurement;Metabolomics;Microfluidics;Molecular Target;Nano-Electrospray;Nigella Sativa;Paclitaxel;Peptides;Performance;Pharmaceutical Preparations;Phase;Plasma;Protein Complex;Protein Metabolite;Proteins;Proteomics;Public Health Relevance;Publications;Reaction;Relative (Related Person);Reproducibility;Research;Research Personnel;Response;Sampling;Sensitivity And Specificity;Serum Albumin;Signal Transduction;Silicon;Small Business Innovation Research Grant;Small Molecule;Solvents;Source;Stem Cell Biology;Stoichiometry;Technology;Therapeutic Effect;Time;Tissues;Toxic Effect;Validation;Variant;Walkers;Warfarin;Whole Blood;Work;

Natural products are rich sources for potential drugs. To accelerate drug discovery from natural products, it is imperative to identify their molecular targets, and mechanistically elucidate their bioavailability, toxicity, and therapeutic effects. However, there remain several challenges in the field. Among them, there is currently no technical platform that could perform mechanistic studies from the "hits" to "leads" using the small volumes of samples that are typically encountered in quantitative high-throughput screening or obtained from biological and clinical studies. To tackle these challenges and in response to RFA-AT-16-003, Newomics Inc. proposes to complete development of its product, a multiomics platform for high-throughput and high-content bioassays of natural products. The Phase II project is built upon the promising results generated from our Phase I project. In Phase I, we have developed ESI-MS assays to screen the interactions between molecular targets and natural products from libraries with different complexity. In Phase II, we will complete development of multiomics assays for commercialization, through working closely with industry partners, academic collaborators, and business consultants. Once developed, Newomics' Omics-chip may become a universal platform for high-throughput identification of molecular targets of natural products in the blood or other tissues, and lay a new foundation for drug discovery and development.

Public Health Relevance Statement:
PUBLIC HEALTH RELEVANCE Cutting-edge technologies enable breakthroughs in biomedical research. Developments of innovative and integrated mass spectrometry-based microfluidic chips will accelerate the high-throughput identification and validation of molecular targets of natural products, thereby contributing to new drug discovery and development.

Project Terms:
analog; base; Binding; Bioinformatics; Biological; Biological Assay; Biological Availability; Biomedical Research; Blood; Blood Cells; Blood specimen; Businesses; Cell Line; Clinical Research; Collaborations; commercialization; Communities; Coupled; Crude Extracts; Databases; Development; Diabetes Mellitus; Diabetic mouse; Diagnosis; Disease Progression; drug development; drug discovery; Drug Kinetics; Foundations; high throughput screening; Human; in vivo; industry partner; innovation; insight; KRAS2 gene; Laboratories; Libraries; Liquid Chromatography; Malignant Neoplasms; mass spectrometer; Mass Spectrum Analysis; metabolome; metabolomics; Microfluidic Microchips; Mississippi; Molecular Target; Monitor; mouse model; Natural Products; next generation; novel therapeutics; operation; Pathway interactions; Performance; Pharmaceutical Preparations; Phase; Plants; Preparation; Proteins; Proteome; Proteomics; public health relevance; Publishing; Reporting; research and development; response; Resveratrol; Sampling; screening; Sensitivity and Specificity; Serum Albumin; Silicon; Small Business Innovation Research Grant; Source; Spectrometry, Mass, Electrospray Ionization; Technology; Therapeutic Effect; therapeutic evaluation; Tissues; Toxic effect; treatment response; Universities; Validation; Vendor; Walkers; Work