ACS Award for Creative Invention: Richard B. Silverman

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Richard B. Silverman, PhD

Patrick G. Ryan/Aon Professor
Professor of Chemistry and Molecular Biosciences, Weinberg School of Arts and Sciences

Member, Chemistry of Life Processes Institute
Director, The Chemistry of Life Processes Institute Predoctoral Training Program

Professor Richard B. Silverman is the inaugural Patrick G. Ryan/Aon Professor. Over the last 42 years at Northwestern University he has developed numerous projects related to the synthesis and evaluation of a variety of enzyme inhibitors and activators, particularly related to neurodegenerative and neurological diseases and cancer. One of the projects was very successful: he is the inventor of LyricaTM, a blockbuster drug marketed by Pfizer for epilepsy, fibromyalgia, and neuropathic pain. He currently has a GABA aminotransferase inactivator (CPP-115) that completed a Phase I clinical trial showing no adverse effects; inhibitors of protein aggregation and toxicity from mutant SOD1 that are active in an ALS mouse model; inactivators of ornithine aminotransferase for hepatocellular carcinoma; selective inhibitors of neuronal nitric oxide synthase (nNOS) that are undergoing preclinical studies for cerebral palsy; novel antagonists for the CaV1.3 pore of a calcium channel targeted for Parkinson’s disease; and compounds for use in enzyme replacement therapy for Gaucher’s disease. Several inhibitors of nNOS have also been found to be active against melanoma and others, in combination with antibiotics, as antibacterial agents. Professor Silverman is the author or co-author of over 370 publications and holds 100 patents to date. The third edition of his textbook, The Organic Chemistry of Drug Design and Drug Action, was published by Elsevier/Academic Press in 2014.

Publications

Cinelli, M. A.; Li, H.; Chreifi, G.; Poulos, T. L.; Silverman, R. B. Nitrile In The Hole: Discovery of a Small Auxiliary Pocket in Neuronal Nitric Oxide Synthase Leading to the Development of Potent and Selective 2-Aminoquinoline Inhibitors. J. Med. Chem., 2017, 60(9), 3958-3978.

Zheng, J.; Chen, L.; Schwake, M.; Silverman, R. B.; Krainc, D. Design and synthesis of potent quinazolines as selective b-glucocerebrosidase modulators. J. Med. Chem. 201659, 8508-8520.

Zigmond, E.; Ya’acov, A. B.; Lee, H.; Lichtenstein, Y.; Shalev, Z.; Smith, Y.; Zolotarov, L.; Ziv, E.; Kalman, R.; Le, H. V.; Lu, H.; Silverman, R. B.; Ilan, Y. Suppression of hepatocellular carcinoma by inhibition of overexpressed ornithine aminotransferase. ACS Med. Chem. Lett. 20156, 840-844.

Le, H. V.; Hawker, D. D.; Wu, R.; Doud, E.; Widom, J.; Sanishvili, R.; Liu, D.; Kelleher, N. L.; Silverman, R. B. Design and mechanism of tetrahydrothiophene-based GABA aminotransferase inactivators. J. Am. Chem. Soc. 2015137, 4525-4533.

Lee, H.; Doud, E. H.; Wu, R.; Sanishvili, R.; Juncosa, J. I.; Liu, D.; Kelleher, N. L.; Silverman, R. B. Mechanism of inactivation of g-aminobutyric acid aminotransferase by (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115). J. Am. Chem. Soc. 2015137, 2628-2640.

Trippier, P. C.; Zhao, K. T.; Fox, S. G.; Schiefer, I. T.; Benmohamed, R.; Moran, J.; Kirsch, D. R.; Morimoto, R. I.; Silverman, R. B. Proteasome Activation is a Mechanism for Pyrazolone Small Molecules Displaying Therapeutic Potential in Amyotrophic Lateral Sclerosis. ACS Chem. Neurosci. 20145, 823-829.

Select Honors and Awards

2017 Creative Invention Award of the American Chemical Society
2014 Fellow of the National Academy of Inventors
2014 Northwestern University Trustee Medal for Faculty Innovation and Entrepreneurship
2014 iCON Innovator Award (iBIO Institute)
2014 Elected to American Academy of Arts & Sciences
2014 Excellence in Medicinal Chemistry Prize of the Israel Chemical Society
2013 Fellow of the Royal Society of Chemistry (UK)
2013 Centenary Prize of the Royal Society of Chemistry
2013 Bristol-Myers Squibb-Edward E. Smissman Award of the American Chemical Society
2013 Roland T. Lakey Award from Wayne State University
2012 Sato Memorial International Award of the Pharmaceutical Society of Japan
2011 Fellow of the American Chemical Society
2011 E. B. Hershberg Award for Important Discoveries in Medicinally Active Substances of the ACS
2011 Alumni Hall of Fame, Central High School of Central High School of Philadelphia
2009 Medicinal Chemistry Hall of Fame of the American Chemical Society
2009 Perkin Medal, Society of Chemical Industry
2008 Alumni Fellow Award, Pennsylvania State University
2003 Arthur C. Cope Senior Scholar Award of the American Chemical Society
1990 Fellow of the American Association for the Advancement of Science