Summary The metabolome is a measure of the output of biological pathways and, as such, is often considered more representative of the functional state of a cell than other ‘omics measures such as genomics or proteomics. In addition, metabolites are conserved across various animal species, facilitating the extrapolation of research findings in laboratory animals to humans. Despite early promise, challenges remain before the full potential of metabolomics can be realized – including the limited availability of high quality metabolite standards and of companies/core facilities that provide metabolomics services. The NIH Common Fund is currently developing a multi-component program to help increase metabolomics research capacity. SBIR contracts that focus on identifying and synthesizing reliable metabolite standards will complement this effort by attracting current and emerging small businesses to develop these much needed tools – which in turn will contribute towards achieving an important NIH Common Fund goal of increasing the repertoire of high quality and authentic standards for identification, characterization and quantization of metabolites. Entities that wish to compete for such contracts must be cognizant of the current cost and intellectual property rights challenges that have restricted the use of said tools in basic, pre-clinical, and translational research alike and consequently make reasonable efforts to make said standards and corresponding product sheets widely accessible to the metabolomics community at large. Project Goals The short and long-term project goals involve the development of both isotopically labeled (i.e., 15N, 13C or 2H) and unlabeled metabolite standards for use with mass spectrometry (MS) and/or nuclear magnetic resonance spectroscopy (NMR), respectively. Compounds need to be synthesized in GLP labs with ISO 9000 certification, and purified by either chromatographic methods or crystallization to >95% purity. Classes of metabolites that require standards for metabolite identification include, but are not limited to: 1. Glycolytic and other energy intermediates 2. Amino acid metabolism 3. Lipids (phospholipids, glycerolipids, sphingolipids, glycolipids, oxylipins) 4. Acylcarnitines and acylglycines 5. Secondary drug metabolites 6. Secondary food metabolites 7. Fatty acids Offerors should focus their proposals on developing at least one set of metabolite standards, where all compounds in the set are linked to one cancer-related metabolic pathway Phase I Activities and Expected Deliverables • Synthesize, as appropriate for any given metabolic pathway, a range of 10-1000 labeled or unlabeled compounds under GLP conditions on a pilot scale sufficient to run at least 10 MS or NMR analyses • Verify structures of the synthesized compounds • Purify compounds using either chromatographic methods or crystallization to >95% purity • Investigate formulation issues and whether the compounds in the metabolite standards set can stably be packaged together versus separately • Run pilot MS or NMR validation tests of the metabolite standards set to evaluate its performance Phase II Activities and Expected Deliverables • Scale up of synthesis, purification, and formulation/packaging/chemical stability of Phase I deliverables to allow for more extensive product validation. • Validate the metabolite standards set for reproducible performance in MS or NMR as appropriate. • Provide letters of interest from potential customers, and later letters of commitment from customers to purchase the product developed under this contract.