Duane D. Miller, PhD
Van Vleet Professor
Department of Pharmaceutical Sciences
The University of Tennessee Health Science Center
227c Johnson Building
847 Monroe Avenue
Memphis, TN 38163
Tel: (901) 448-6026
Fax: (901) 448-6828
Email: Duane D. Miller
- PhD Institution: University of Washington, Medicinal Chemistry Department
The design, synthesis and characterization of new drug molecules for mechanism based structure-activity relationships is the primary focus of our laboratory. One of the important areas of research is studying new drugs affecting the central and peripheral nervous systems. Our laboratory is very interested in the design of drugs that are used to treat asthma, emphysema and obesity. Other areas of keen interest are drugs used to treat and diagnose prostate cancer and diabetic complications.
We are currently investigating the modification of a molecule called trimetoquinol which is used in Japan. We are attempting to make chemical structural changes in the molecule so that it can be used to activate selectively beta 2-adrenergic receptors found in lung tissue. We are also attempting to make changes that will also convert this same molecule into a beta 3-adrenergic receptor agonist for the treatment of obesity. The latter receptors are found in adipose tissue and upon activation lead to the breakdown of fat. We are also in the process of studying medetomidine, an alpha-adrenergic agonist. We are changing the structure of medetomidine chemically to see if such changes can lead to a better understanding of how this molecule binds to the various subtypes of a- adrenergic receptors.
We are very interested in drugs that could interfere with the craving for cocaine. We are now synthesizing drugs that will block specific glutamate receptors found in the brain and hopefully such new information will help us find an agent that will be useful in treating cocaine addiction.
Drugs that bind to androgen receptors and their relationship to prostate cancer are being studied in our laboratory. A major project is directed toward synthesizing new radiolabeled androgen ligands and we plan to use this technology towards imaging metastatic prostate cancer.
A major enzyme in the development of diabetic complications such as cataracts is thought to be the enzyme aldose reductase. Our laboratory has developed irreversible inhibitors for studying this enzyme.
- Ponnusamy S, Tran QT, Harvey I, Smallwood HS, Thiyagarajan T, Banerjee S, Johnson DL, Dalton JT, Sullivan RD, Miller DD, Bridges D, Narayanan R. Pharmacologic activation of estrogen receptor β increases mitochondrial function, energy expenditure, and brown adipose tissue. FASEB J. 2016 Oct 12. pii: fj.201600787RR. PubMed PMID: 27733447.
- Lin Z, Marepally SR, Ma D, Kim TK, Oak AS, Myers LK, Tuckey RC, Slominski AT, Miller DD, Li W. Synthesis and Biological Evaluation of Vitamin D3 Metabolite 20S,23S-Dihydroxyvitamin D3 and Its 23R Epimer. J Med Chem. 2016 May 26;59(10):5102-8. doi: 10.1021/acs.jmedchem.6b00182. PubMed PMID: 27070779.
- Lin Z, Marepally SR, Kim TK, Janjetovic Z, Oak AS, Postlethwaite AE, Myers LK, Tuckey RC, Slominski AT, Miller DD, Li W. Design, Synthesis and Biological Activities of Novel Gemini 20S-Hydroxyvitamin D3 Analogs. Anticancer Res. 2016 Mar;36(3):877-86. PubMed PMID: 26976974.
- Pi M, Kapoor K, Wu Y, Ye R, Senogles SE, Nishimoto SK, Hwang DJ, Miller DD, Narayanan R, Smith JC, Baudry J, Quarles LD. Structural and Functional Evidence for Testosterone Activation of GPRC6A in Peripheral Tissues. Mol Endocrinol. 2015 Dec;29(12):1759-73. doi: 10.1210/me.2015-1161. PubMed PMID: 26440882; PubMed Central PMCID: PMC4664231.
- Wang Q, Lin Z, Kim TK, Slominski AT, Miller DD, Li W. Total synthesis of biologically active 20S-hydroxyvitamin D3. Steroids. 2015 Dec;104:153-62. doi: 10.1016/j.steroids.2015.09.009. PubMed PMID: 26433048; PubMed Central PMCID: PMC4659745.
- Hwang DJ, Wang J, Li W, Miller DD. Structural Optimization of Indole Derivatives Acting at Colchicine Binding Site as Potential Anticancer Agents. ACS Med Chem Lett. 2015 Aug 6;6(9):993-7. doi: 10.1021/acsmedchemlett.5b00208. PubMed PMID: 26396686; PubMed Central PMCID: PMC4569884.