This application requests funding to acquire a Q-TOF mass spectrometer to replace the mass spectrometer component of an 18-year-old Bruker Esquire-LC/MS system, which is an essential part of the Shared Instrument Facility in the Department of Pharmaceutical Sciences at the University of Tennessee Health Science Center (UTHSC). The Bruker Esquire-LC/MS system has been well maintained and is the work horse supporting extensive small-molecular drug discovery and drug delivery programs at UTHSC in the areas of cancer, obesity, diabetes, radiation protection, radiation mitigation, bacteria inflection, and inflammation diseases. Several small-molecule drug candidates have been licensed for commercial development, including one currently in Phase III clinical trials. However, the age of the current mass spectrometer has resulted in more and more frequent breakdowns in recent years. Bruker officially stopped technical support for this type of instrument system in early 2010. Repair parts are scarce and have become very expensive. The proposed new Q-TOF mass spectrometer will replace the now unreliable mass spectrometer component of the Bruker Esquire-LC/MS system. This powerful new mass spectrometer will benefit more than 10 principal investigators supported by nine R01s, one RC2, one R33, three R21s, and other sources of support. The Q-TOF mass spectrometer will provide years of reliable accessibility, greater sensitivity in both MS and MS/MS modes, and the capability to obtain accurate mass for more efficient structure elucidation. This state-of-the-art instrument wil support drug discovery in preclinical development by using novel small molecules and their translation to innovative therapies for a variety of diseases. UTHSC is strongly committed to supporting biomedical research. The College of Pharmacy will provide $25,000 as a cost share for the purchase of the new instrument, fully support a staff scientist to maintain the Shared Instrument Facility, and assume all future maintenance and repair cost after the warranty period without charging user fees. An advisory committee will ensure effective utilization of the instrument and adequate access by the major users, other NIH-supported investigators, new investigators, and investigators with early-stage projects.

Public Health Relevance

The Q-TOF mass spectrometer requested will replace a technologically limited Esquire-LC/MS mass spectrometer that is nearly two decades old and will provide reliable and sophisticated support for 20 currently funded projects important to human health. These projects focus on small-molecule drug discovery and drug delivery in the areas of cancer, obesity, diabetes, radiation protection, radiation mitigation, bacteria inflection and inflammation diseases.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10OD010678-01
Application #
8246986
Study Section
Special Emphasis Panel (ZRG1-BCMB-P (30))
Program Officer
Birken, Steven
Project Start
2012-05-01
Project End
2013-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
1
Fiscal Year
2012
Total Cost
$325,000
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Lin, Zongtao; Yang, Ruinan; Guan, Zheng et al. (2014) Ultra-performance LC separation and quadrupole time-of-flight MS identification of major alkaloids in Plumula Nelumbinis. Phytochem Anal 25:485-94
Slominski, Andrzej T; Kim, Tae-Kang; Takeda, Yukimasa et al. (2014) ROR? and ROR ? are expressed in human skin and serve as receptors for endogenously produced noncalcemic 20-hydroxy- and 20,23-dihydroxyvitamin D. FASEB J 28:2775-89
Chen, Jianjun; Wang, Jin; Schwab, Luciana P et al. (2014) Benzimidazole analogs as potent hypoxia inducible factor inhibitors: synthesis, biological evaluation, and profiling drug-like properties. Anticancer Res 34:3891-904
Slominski, Andrzej T; Zmijewski, Michal A; Semak, Igor et al. (2014) Cytochromes p450 and skin cancer: role of local endocrine pathways. Anticancer Agents Med Chem 14:77-96
Lu, Yan; Chen, Jianjun; Wang, Jin et al. (2014) Design, synthesis, and biological evaluation of stable colchicine binding site tubulin inhibitors as potential anticancer agents. J Med Chem 57:7355-66
Slominski, Andrzej T; Kim, Tae-Kang; Shehabi, Haleem Z et al. (2014) In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland. Mol Cell Endocrinol 383:181-92
Wang, Jin; Li, Wei (2014) Discovery of novel second mitochondria-derived activator of caspase mimetics as selective inhibitor of apoptosis protein inhibitors. J Pharmacol Exp Ther 349:319-29
Wang, Jin; Chen, Jianjun; Miller, Duane D et al. (2014) Synergistic combination of novel tubulin inhibitor ABI-274 and vemurafenib overcome vemurafenib acquired resistance in BRAFV600E melanoma. Mol Cancer Ther 13:16-26
Chen, Jianjun; Wang, Jin; Kim, Tae-Kang et al. (2014) Novel vitamin D analogs as potential therapeutics: metabolism, toxicity profiling, and antiproliferative activity. Anticancer Res 34:2153-63
Xiao, Min; Ahn, Sunjoo; Wang, Jin et al. (2013) Discovery of 4-Aryl-2-benzoyl-imidazoles as tubulin polymerization inhibitor with potent antiproliferative properties. J Med Chem 56:3318-29

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