Editorial page, special issue honoring Professor Mark Cushman.

Abstract

This issue of Medicinal Research Reviews is dedicated to an accomplished scientist and excellent mentor, Dr. Mark Cushman, Distinguished Professor of Medicinal Chemistry in the Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University. Professor Cushman completed 2 years of pre-pharmacy studies in 1965 at Fresno State College (now California State University, Fresno). Thereafter, he received a Doctor of Pharmacy degree (1969) and a Ph.D. in Medicinal Chemistry (1973) both from the University of California San Francisco. As a graduate student, he worked under the direction of Dr. Neal Castagnoli, Jr. During his graduate studies, he focused on the development of organic methodology and the synthesis of tetrahydrocannabinol. A highlight of his graduate work is the condensation of Schiff bases with succinic anhydrides—now known as the Castagnoli-Cushman reaction. Upon graduation, he moved to Massachusetts Institute of Technology (MIT) to perform research in the laboratory of George Büchi, Ph.D. In 1975 he joined the College of Pharmacy of Purdue University as an assistant professor and he rose through the ranks to his current position as a Distinguished Professor of Medicinal Chemistry. Dr. Cushman and his research group have made seminal contributions to the broad field of medicinal chemistry. He is primarily known for his work on developing small-molecule therapeutics against cancer, especially indenoisoquinolines and other noncamptothecin inhibitors of topoisomerase 1. He has over 340 published papers and 39 patents, some of which have been licensed to private companies for further development. Currently, three drug candidates from his lab are undergoing clinical trials. Dr. Cushman has also made important contributions to the discovery of inhibitors of tyrosyl-DNA phosphodiesterase 1 and retinoid X receptor activators. In addition, his group has published pivotal papers on the synthesis and evaluation of nonnucleoside reverse transcriptase and riboflavin synthase inhibitors. His group has also been very active in the synthesis of natural products including nitidine chloride, coryladine, (±)-rhalictricavine, berlambine, (±)-canadine, chelidonine, and Abyssinian. His work is characterized by both a high level of detail and careful attention to mechanistic insights to understand chemical and biological functions. Professor Cushman has received various awards including the Philip S. Portoghese Joint Lectureship sponsored by the Journal of Medicinal Chemistry and the ACS Division of Medicinal Chemistry (2018), the Ole Gisvold Lectureship in Medicinal Chemistry from the Department of Medicinal Chemistry at the University of Minnesota (2018), the University of California San Francisco 150th Anniversary Alumni Excellence Award (2015), and the Webster-Sibilsky Lecturer, University of Illinois (2012). He is a Fellow of the American Association for the Advancement of Science (2012), a senior Fulbright Scholar (1983-1984), and currently serves as an Associate Editor for the Journal of Medicinal Chemistry. He is also a member of the Board of Directors of Gibson Oncology. He was recently selected as a Fellow of the National Academy of Inventors (2018) and as a Highly Prolific Author by the Journal of Medicinal Chemistry (2017). This issue hopes to honor his broad contributions to the fields of organic and medicinal chemistry. The reviews presented herein try to highlight (although not in an extensive way), some of the most important scientific accomplishments made by Dr. Cushman and his group. Even though his papers and patents clearly indicate his impact in the field, publications do not do justice to his scientific contributions. Dr. Cushman is an example of hard work, enthusiasm, and dedication. He set the bar very high for all of his 39 graduate students and 64 postdocs and visiting scholars by being in the laboratory early and leaving late. He demanded excellence from others but always did the same of himself. He is detail-oriented, a perfectionist who always made sure research was done at a high level and with integrity, ethics, and honesty above everything else. He loves organic and medicinal chemistry and would make sure that each of his students and trainees understood the mechanism of a reaction and the mode of action of their compounds. The best thing, and I can speak for each one my labmates, is that Dr. Cushman allowed us to fail. He usually knew what reaction was going to work and which one would not. However, he would give us the freedom to try and to experiment. He would review the problem, analyze the data, and guide us in the right direction but would make sure we were the ones finding the answer to the problem (which of course, he sometimes knew before the process even started). This mentoring style helped us to grow as scientists and to become the best we could be. It has been my pleasure to coordinate this issue and see a glimpse of just how far his research—and his positive influence—has extended.