This shared instrumentation application is for an AB Sciex Triple Quad 4500 triple quadrupole mass spectrometer as replacement for an outdated shared liquid chromatography-mass spectrometry instrument. Major research efforts at the University of Tennessee Health Science Center Colleges of Pharmacy and Medicine are directed towards the development of new molecular entities for unmet medical needs. The requested instruments supports 9 investigators with 14 research projects (10 NIH-supported) focused on small molecule drug discovery and development. Targeted indications include the treatments of a variety of cancer types, tuberculosis, radiation injury, and other conditions. Crucial assessments in early drug discovery and lead optimization include the investigation of the lead compounds'chemical and metabolic stability, biopharmaceutical and pharmacokinetic properties. The requested instrument will be utilized for the quantification of small molecule drug candidates in biologic matrices in support of these studies. Due to its high sensitivity compared to other LC-MS/MS equipment, it will allow the reliable quantification of the usually low pharmacologically active concentrations of highly potent drug candidates.
Major research efforts at the University of Tennessee Health Science Center Colleges of Pharmacy and Medicine are directed towards the discovery and development of small molecule drugs for unmet medical needs, including cancer, tuberculosis, and radiation injury. This application requests funds for the acquisition of a triple quadrupole mass spectrometer that will be used in the lead compound discovery and iterative optimization process in order to produce drug candidates viable for further preclinical and clinical development.
|Santos, Karen; Lukka, Pradeep B; Grzegorzewicz, Anne et al. (2018) Primary Lung Dendritic Cell Cultures to Assess Efficacy of Spectinamide-1599 Against Intracellular Mycobacterium tuberculosis. Front Microbiol 9:1895|
|Liu, Jiuyu; Bruhn, David F; Lee, Robin B et al. (2017) Structure-Activity Relationships of Spectinamide Antituberculosis Agents: A Dissection of Ribosomal Inhibition and Native Efflux Avoidance Contributions. ACS Infect Dis 3:72-88|
|Midde, Narasimha M; Sinha, Namita; Lukka, Pradeep B et al. (2017) Alterations in cellular pharmacokinetics and pharmacodynamics of elvitegravir in response to ethanol exposure in HIV-1 infected monocytic (U1) cells. PLoS One 12:e0172628|
|He, Hui; Ma, Dejian; Crone, Laura Brooks et al. (2017) Assessment of the Drug-Drug Interaction Potential Between Theacrine and Caffeine in Humans. J Caffeine Res 7:95-102|
|Seleverstov, Olga; Tobiasz, Ana; Jackson, J Scott et al. (2017) Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors. Alcohol 61:51-61|
|Midde, Narasimha M; Gong, Yuqing; Cory, Theodore J et al. (2017) Influence of Ethanol on Darunavir Hepatic Clearance and Intracellular PK/PD in HIV-Infected Monocytes, and CYP3A4-Darunavir Interactions Using Inhibition and in Silico Binding Studies. Pharm Res 34:1925-1933|
|Madhura, Dora Babu; Trivedi, Ashit; Liu, Jiuyu et al. (2016) Tissue Penetration of a Novel Spectinamide Antibiotic for the Treatment of Tuberculosis. AAPS J 18:788-91|
|Midde, Narasimha M; Rahman, Mohammad A; Rathi, Chetan et al. (2016) Effect of Ethanol on the Metabolic Characteristics of HIV-1 Integrase Inhibitor Elvitegravir and Elvitegravir/Cobicistat with CYP3A: An Analysis Using a Newly Developed LC-MS/MS Method. PLoS One 11:e0149225|
|Madhura, Dora B; Liu, Juiyu; Meibohm, Bernd et al. (2016) Phase II Metabolic Pathways of Spectinamide Antitubercular Agents: A Comparative Study of the Reactivity of 4-Substituted Pyridines to Glutathione Conjugation. Medchemcomm 7:114-117|