Grants per year
Personal profile
Research Interests
The research in Professor Silverman’s group can be summarized as investigations of the molecular mechanisms of action, rational design, and syntheses of potential medicinal agents. The primary focus is basic research into central nervous system disorders, including Parkinson’s disease, cerebral palsy, amyotrophic lateral sclerosis, addiction, and epilepsy. Other therapeutic areas include cancer (melanoma and hepatocellular carcinoma), lysosomal storage diseases, such as Gaucher’s disease, and bacterial infection. Numerous drugs are known to function as specific inhibitors of particular enzymes. For some enzyme targets, where potent reversible inhibitors are desired, computer modeling based on X-ray crystal structures initiates the research (high-throughput screening also may be used). For enzyme targets where inactivators are desired and when little is known about the enzyme’s molecular mechanism of action, chemical model studies are designed to determine reasonable nonenzymatic pathways applicable to the enzyme. For those enzymes, mechanism-based inactivators are designed and synthesized and inactivation mechanisms investigated. The enzymes are isolated from either mammalian tissue or from overexpressed cells containing recombinant enzymes. Collaborations are developed in X-ray crystallography and preclinical studies.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
Organic Chemistry, PhD, Harvard University
… → 1974
Chemistry, BS, Pennsylvania State University
… → 1968
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Collaborations and top research areas from the last five years
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Investigations of the protein aggregation inhibitor NU-9 and its derivatives: mode of action and impact on Alzheimer’s disease and related dementias
Klein, W. L. (PD/PI), Ozdinler, H. (PD/PI) & Silverman, R. B. (PD/PI)
9/30/24 → 7/31/29
Project: Research project
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New Inactivators of GABA Aminotransferase for Epilepsy and Neuropathic Pain
Silverman, R. B. (PD/PI) & Silverman, R. B. (PD/PI)
National Institute of Neurological Disorders and Stroke
7/15/21 → 6/30/26
Project: Research project
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Ornithine Aminotransferase Inactivation, a New Approach for Treatment of Cancers
Silverman, R. B. (PD/PI) & Silverman, R. B. (PD/PI)
4/15/21 → 3/31/26
Project: Research project
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CardioExcyte 96 System for Pharmacology Research at Northwestern University
George, A. L. (PD/PI), Abdulkadir, S. A. (Other), Ardehali, H. (Other), Arora, R. K. (Other), Burridge, P. (Other), Kearney, J. A. (Other), McNally, E. M. (Other), Schiltz, G. E. (Other), Silverman, R. B. (Other), Watterson, D. M. (Other) & Wilsbacher, L. D. (Other)
Office of the Director, National Institutes of Health
6/15/20 → 6/30/25
Project: Research project
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Crosstalk Between nNOS/NO and COX-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression
Patel, A., Tong, S., Roosan, M. R., Syed, B., Awasthi, A., Silverman, R. B. & Yang, S., Feb 2025, In: Cancers. 17, 3, 477.Research output: Contribution to journal › Article › peer-review
Open Access -
Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction
Wirt, J. L., Ferreira, L. A., Alves Jesus, C. H., Woodward, T. J., Oliva, I., Xu, Z., Crystal, J. D., Pepin, R. H., Silverman, R. B. & Hohmann, A. G., Jan 7 2025, In: Proceedings of the National Academy of Sciences of the United States of America. 122, 1, e2318833121.Research output: Contribution to journal › Article › peer-review
Open Access -
Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases
Johnson, E. A., Nowar, R., Viola, K. L., Huang, W., Zhou, S., Bicca, M. A., Zhu, W., Kranz, D. L., Klein, W. L. & Silverman, R. B., Mar 11 2025, In: Proceedings of the National Academy of Sciences of the United States of America. 122, 10, e2402117122.Research output: Contribution to journal › Article › peer-review
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Protection against Amyloid-β Aggregation and Ferroptosis/Oxytosis Toxicity by Arylpyrazolones: Alzheimer’s Disease Therapeutics
Soares, P., Rahaman, M., Maher, P. & Silverman, R. B., Feb 13 2025, In: ACS Medicinal Chemistry Letters. 16, 2, p. 294-300 7 p.Research output: Contribution to journal › Article › peer-review
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Synthesis of Oxabicyclo[3.2.1]octan-3-ol Scaffold via Burgess Reagent Mediated Cyclodehydration of δ-Diols under Acidic Conditions
Elmansy, M. F., dos Remedios, J. R. D. & Silverman, R. B., Jan 17 2025, In: Organic Letters. 27, 2, p. 640-644 5 p.Research output: Contribution to journal › Article › peer-review
Datasets
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Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(5-(3-(dimethylamino)propyl)-2,3,4-trifluorophenethyl)-4-methylpyridin-2-amine
Do, H. T. (Contributor), Li, H. (Contributor), Chreifi, G. (Contributor), Poulos, T. L. (Contributor) & Silverman, R. B. (Contributor), Protein Data Bank (PDB), Mar 13 2019
DOI: 10.2210/pdb6NH8/pdb, https://www.wwpdb.org/pdb?id=pdb_00006nh8
Dataset
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Structure of Bacillus subtilis Nitric Oxide Synthase in complex with 7-((2-((Methylamino)methyl)phenoxy)methyl)quinolin-2-amine
Holden, J. K. (Contributor), Lewis, M. C. (Contributor), Cinelli, M. A. (Contributor), Abdullatif, Z. (Contributor), Pensa, A. V. (Contributor), Silverman, R. B. (Contributor) & Poulos, T. L. (Contributor), Protein Data Bank (PDB), Sep 21 2016
DOI: 10.2210/pdb5G6G/pdb, https://www.wwpdb.org/pdb?id=pdb_00005g6g
Dataset
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Human Ornithine Aminotransferase cocrystallized with its inhibitor, (S,E)-3-amino-4-(fluoromethylene)cyclopent-1-ene-1-carboxylate
Zhu, W. (Contributor), Butrin, A. (Contributor), Melani, R. D. (Contributor), Doubleday, P. F. (Contributor), Ferreira, G. M. (Contributor), Tavares, M. T. (Contributor), Habeeb Mohammad, T. S. (Contributor), Beaupre, B. A. (Contributor), Kelleher, N. L. (Contributor), Moran, G. R. (Contributor), Liu, D. (Contributor) & Silverman, R. B. (Contributor), Protein Data Bank (PDB), Apr 6 2022
DOI: 10.2210/pdb7TED/pdb, https://www.wwpdb.org/pdb?id=pdb_00007ted
Dataset
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Structure of Bacillus subtilis Nitric Oxide Synthase in complex with two molecules of 7-((3-Fluorophenethylamino)ethyl)quinolin-2-amine
Holden, J. K. (Contributor), Lewis, M. C. (Contributor), Cinelli, M. A. (Contributor), Abdullatif, Z. (Contributor), Pensa, A. V. (Contributor), Silverman, R. B. (Contributor) & Poulos, T. L. (Contributor), Protein Data Bank (PDB), Sep 21 2016
DOI: 10.2210/pdb5G6B/pdb, https://www.wwpdb.org/pdb?id=pdb_00005g6b
Dataset
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Structure of rat neuronal nitric oxide synthase heme domain in complex with 6-(3-(3-(dimethylamino)propyl)-2,5-difluorophenethyl)-4-methylpyridin-2-amine
Do, H. T. (Contributor), Li, H. (Contributor), Chreifi, G. (Contributor), Poulos, T. L. (Contributor) & Silverman, R. B. (Contributor), Protein Data Bank (PDB), Mar 13 2019
DOI: 10.2210/pdb6NGU/pdb, https://www.wwpdb.org/pdb?id=pdb_00006ngu
Dataset