Dear Colleagues,

This Special Issue of Molecules is dedicated to Professor Duane D Miller, a member of the National Academy of Investors (NAI) and Professor Emeritus at College of Pharmacy, University of Tennessee Health Science Center, for his work in small molecule drug discovery and development.

Dr. Miller was born in 1943, and grew up on a farm in Larned, Kansas. He obtained his B.S. degree in Pharmacy at Kansas University in 1966, and his interest in research was stimulated by two professors at the University of Kansas, Dr. Ed Smissman and Dr. Matt Mertes. As a National Science Foundation Undergraduate Research Fellow, he worked on anticancer drugs. He next moved to Seattle, Washington, and was an NIH Fellow while at the University of Washington, where he obtained his Ph.D. in Medicinal Chemistry, in 1969, under the mentorship of Dr. Wendel L. Nelson for his research on conformationally restricted analogs of ephedrine. He next joined the Ohio State University Faculty in 1969, where he became Professor and Chairman of the Division of Medicinal Chemistry and Pharmacognosy in 1982. He had a highly synergistic collaboration with his colleagues in elucidating steric interactions of imidazolines, catecholamines, and tetrahydroisoquinolines with adrenoceptors. The classic studies provided the foundation for understanding the molecular components underlying the efficacy of agonists on adrenergic receptors. He studied dopamine and norepinephrine analogs with Drs. Popat Patil, Norman Uretsky and Dennis Feller. They were the first to discovered a set of imidazoline chiral agents that did not follow the Easson–Stedman theory (1933), which states that optically active adrenergic agonists possessing an asymmetric hydroxyl-substituted benzylic carbon atom will have the following relative potencies: R(−) > than S(+) = desoxy form of drugs binding to the adrenergic receptors. He moved to the University of Tennessee Health Science Center in Memphis, TN, in 1992, as the Van Vleet Endowed Professor of The Department of Pharmaceutical Sciences in the College of Pharmacy. He was made chair of the Department of Pharmaceutical Sciences in 2001.

Dr. Miller has published over 450 publications and 16 book chapters. He has given 343 presentations at national and international meetings and holds over 100 patents and patent applications. Dr. Miller’s research interests include the design and synthesis of new drug molecules. He has a strong interest in developing drugs for new areas in which there is currently a lack of therapeutic agents or in areas in which there is the need to develop new drugs with fewer side effects. Dr. Miller and Dr. Jim Dalton, currently Dean of the College of Pharmacy at the University of Michigan, discovered the first new nonsteroidal selective androgen receptor modulators (SARMs) and reported about them in 1998. GTx is the company that initially licensed SARMs, and has since carried out clinical studies with SARMs. These agents were studied for their use in muscle wasting and osteoporosis in cancer patients. SARMs have the advantage that they are orally active with fewer side effects, including less liver toxicity than current muscle building agents. Such agents may be of value in aging males to treat low testosterone in older males (termed ADAM (androgen decline in aging males) or also referred to as andropause). The SARMs completed Phase I, Phase II, and Phase III human clinical testing for the treatment of cachexia in cancer patients but were not approved by the FDA. Other studies are being attempted to establish a rationale for obtaining approval. Together with Dr. Ramesh Narayanan, new selective androgen receptor degraders (SARDs) were discovered that work to destroy the androgen receptor in treating castration-resistant cancer (CRPC). These latter agents are designed to help patients where regular androgen receptor antagonists have failed in prostate cancer therapy. Dr. Miller and Dr. Narayanan have also recently discovered selective androgen receptor covalent antagonists (SARCAs) that can also potentially be used for prostate cancer. He has also worked on radiation mitigators with Dr. Gabor Tigyi, and these agents are licensed to RxBio along with anti-inflammatory drugs developed with Dr. Ryan Yates. Dr. Miller has worked with Dr. Elden Geisert on drugs for the treatment of brain cancer, resulting in the development of molecules that have been licensed by RxBio.

During his academic career, Dr. Miller has been presented the University of Tennessee National Alumni Outstanding Teacher Award (1994). For teaching at the University of Tennessee Health Science Center at the College of Pharmacy, he was presented the Student Government Association Executive Council (SGAEC) Excellence in Teaching Award in 1995, 2001, and 2005. He was the UT Pharmacy Class Teacher of the Year (2006). He has mentored 29 graduate students and 35 postdoctoral researchers.

Dr. Miller was honored as an American Association Pharmaceutical Scientists (AAPS) Fellow in (1990). He was selected as an American Association for the Advancement of Science (AAAS) Fellow and honored for fundamental studies on the structural and stereochemical requirements of adrenergic drugs interacting in the CNS and peripheral nervous systems (2001). In 2008, he was recognized by the University of Washington, College of Pharmacy, as the “Alumni of the Year”. He was awarded the Division of Medicinal Chemistry Award from the American Chemical Society at the National Medicinal Chemistry Symposium in June 2008. The Division of Medicinal Chemistry Award is conferred biennually in the United States to a scientist or team of scientists with a substantial record of contributions to the field of medicinal chemistry through research, mentorship, and service to the discipline. In August 2008, he was inducted into the Medicinal Chemistry Hall of Fame of the American Chemical Society at the National American Chemical Society Meeting in Philadelphia, Pennsylvania. In 2009, he was awarded the Volwiler Research Achievement Award for research in the pharmaceutical sciences at the National American Association Colleges of Pharmacy (AACP). In 2015, he was inducted into the National Academy of Inventors at the California Institute Technology in Pasadena, California. In 2019, he was honored for being the first to have 100 US patents by the University of Tennessee Research Foundation.

In 2015, he retired and was given the title of Professor Emeritus, and he continues to conduct funded research on the design, preparation, and study of new drugs for the treatment of cancer. He is currently patenting and publishing about new drugs for prostate cancer, breast cancer, melanoma, and brain cancer (glioma) with Dr. Ramesh Narayanan, Dr. Wei Li, and Dr. Lawrence Pfeffer at the University of Tennessee Health Science Center. Dr. Wei Li and Dr. Miller have worked together for over ten years in the area of tubulin inhibitors and have developed a drug, Veu-111, that has been licensed by Veru and is currently in Phase I/II clinical trials for resistant prostate cancer in addition to entering into Phase II studies for treatment of SARS-CoV-2 respiratory distress syndrome in adults.

We are organizing a Special Issue honoring Dr. Miller’s distinguished scientific career over the past 50+ years. This Special Issue will consist of communications, original research articles, and review articles related to small molecule drug discovery and development as well as anecdotes about Dr. Duane Miller.

Prof. Dr. Wei Li
Guest Editor

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