Duane D. Miller, PhD

Education

• PhD Institution: University of Washington, Medicinal Chemistry Department

Research Interests

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.

Representative Publications

• Kashyap VK, Dan N, Chauhan N, Wang Q, Setua S, Nagesh PKB, Malik S, Batra V, Yallapu MM, Miller DD, Li W, Hafeez BB, Jaggi M, Chauhan SC. VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway. Cancer Lett. 2019 Dec 3. pii: S0304-3835(19)30590-7. doi: 10.1016/j.canlet.2019.11.035. [Epub ahead of print] PubMed PMID: 31809801.
• Arnst KE, Banerjee S, Wang Y, Chen H, Li Y, Yang L, Li W, Miller DD, Li W. X-ray Crystal Structure Guided Discovery and Antitumor Efficacy of Dihydroquinoxalinone as Potent Tubulin Polymerization Inhibitors. ACS Chem Biol. 2019 Nov 25. doi: 10.1021/acschembio.9b00696. [Epub ahead of print] PubMed PMID: 31714738.
• Ponnusamy S, He Y, Hwang DJ, Thiyagarajan T, Houtman R, Bocharova V, Sumpter BG, Fernandez E, Johnson D, Du Z, Pfeffer LM, Getzenberg RH, McEwan IJ, Miller DD, Narayanan R. Orally Bioavailable Androgen Receptor Degrader, Potential Next-Generation Therapeutic for Enzalutamide-Resistant Prostate Cancer. Clin Cancer Res. 2019 Nov 15;25(22):6764-6780. doi: 10.1158/1078-0432.CCR-19-1458. Epub 2019 Sep 3. PubMed PMID: 31481513.
• Wang Q, Arnst KE, Wang Y, Kumar G, Ma D, White SW, Miller DD, Li W, Li W. Structure-Guided Design, Synthesis, and Biological Evaluation of (2-(1H-Indol-3-yl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl) Methanone (ABI-231) Analogues Targeting the Colchicine Binding Site in Tubulin. J Med Chem. 2019 Jul 25;62(14):6734-6750. doi: 10.1021/acs.jmedchem.9b00706. Epub 2019 Jul 12. PubMed PMID: 31251599.
• Arnst KE, Wang Y, Lei ZN, Hwang DJ, Kumar G, Ma D, Parke DN, Chen Q, Yang J, White SW, Seagroves TN, Chen ZS, Miller DD, Li W. Colchicine Binding Site Agent DJ95 Overcomes Drug Resistance and Exhibits Antitumor Efficacy. Mol Pharmacol. 2019 Jul;96(1):73-89. doi: 10.1124/mol.118.114801. Epub 2019 May 1. PubMed PMID: 31043459; PubMed Central PMCID: PMC6553560.
• Yang R, Chen H, Guo D, Dong Y, Miller DD, Li W, Mahato RI. Polymeric Micellar Delivery of Novel Microtubule Destabilizer and Hedgehog Signaling Inhibitor for Treating Chemoresistant Prostate Cancer. J Pharmacol Exp Ther. 2019 Sep;370(3):864-875. doi: 10.1124/jpet.119.256628. Epub 2019 Apr 17. PubMed PMID: 30996033; PubMed Central PMCID: PMC6806635.

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