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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New Inactivators of GABA Aminotransferase for Epilepsy and Neuropathic Pain
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
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., Abdulkadir, S. A., Ardehali, H., Arora, R. K., Burridge, P., Kearney, J. A., McNally, E. M., Schiltz, G. E., Silverman, R. B., Watterson, D. M. & Wilsbacher, L. D.
Office of the Director, National Institutes of Health
6/15/20 → 6/30/25
Project: Research project
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Erratum: Rational Design, Synthesis, and Mechanism of (3S,4R)-3-Amino-4-(difluoromethyl)cyclopent-1-ene-1-carboxylic Acid: Employing a Second-Deprotonation Strategy for Selectivity of Human Ornithine Aminotransferase over GABA Aminotransferase (Journal of the American Chemical Society (2022) 144: 12 (5629−5642) DOI: 10.1021/jacs.2c00924)
Zhu, W., Butrin, A., Donadelli Melani, R., Doubleday, P. F., Ferreira, G. M., Tavares, M. T., Habeeb Mohammad, T. S., Beaupre, B. A., Kelleher, N. L., Moran, G. R., Liu, D. & Silverman, R. B., May 3 2023, In: Journal of the American Chemical Society. 145, 17, p. 9895-9896 2 p.Research output: Contribution to journal › Comment/debate › peer-review
Open Access -
Improved synthesis and anticancer activity of a potent neuronal nitric oxide synthase inhibitor
Vasu, D., Reidl, C. T., Wang, E., Yang, S. & Silverman, R. B., Jun 15 2023, In: Bioorganic and Medicinal Chemistry Letters. 90, 129329.Research output: Contribution to journal › Article › peer-review
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Potent, Selective, and Membrane Permeable 2-Amino-4-Substituted Pyridine-Based Neuronal Nitric Oxide Synthase Inhibitors
Vasu, D., Do, H. T., Li, H., Hardy, C. D., Awasthi, A., Poulos, T. L. & Silverman, R. B., Jul 27 2023, In: Journal of Medicinal Chemistry. 66, 14, p. 9934-9953 20 p.Research output: Contribution to journal › Article › peer-review
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Small molecules targeting different cellular pathologies for the treatment of amyotrophic lateral sclerosis
Elmansy, M. F., Reidl, C. T., Rahaman, M., Özdinler, P. H. & Silverman, R. B., 2023, (Accepted/In press) In: Medicinal Research Reviews.Research output: Contribution to journal › Review article › peer-review
Open Access -
Structural and Mechanistic Basis for the Inactivation of Human Ornithine Aminotransferase by (3S,4S)-3-Amino-4-fluorocyclopentenecarboxylic Acid
Shen, S., Butrin, A., Beaupre, B. A., Ferreira, G. M., Doubleday, P. F., Grass, D. H., Zhu, W., Kelleher, N. L., Moran, G. R., Liu, D. & Silverman, R. B., Feb 2023, In: Molecules. 28, 3, 1133.Research output: Contribution to journal › Article › peer-review
Open Access
Datasets
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3NLT : Structure of endothelial nitric oxide synthase heme domain complexed with N1-{(3'S,4'S)-4'-[(6"-amino-4"-methylpyridin-2"-yl)methyl]pyrrolidin-3'-yl}- N2-(3'-fluorophenethyl)ethane-1,2-diamine tetrahydrochloride
Xue, F. (Contributor), Li, H. (Contributor), Delker, S. L. (Contributor), Fang, J. (Contributor), Poulos, T. L. (Contributor) & Silverman, R. B. (Contributor), RCSB-PDB, 2011
DOI: 10.2210/pdb3nlt/pdb, https://www.rcsb.org/structure/3NLT
Dataset
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1P6I : Rat neuronal NOS heme domain with (4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N'-nitroguanidine bound
Li, H. (Contributor), Poulos, T. L. (Contributor), Silverman, R. B. (Contributor), Gómez-Vidal, J. A. (Contributor), Flinspach, M. L. (Contributor), Jamal, J. (Contributor), Yang, W. (Contributor), Huang, H. (Contributor), Hah, J. (Contributor) & Litzinger, E. A. (Contributor), RCSB-PDB, 2004
DOI: 10.2210/pdb1p6i/pdb, https://www.rcsb.org/structure/1P6I
Dataset
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2QB2 : Structural Studies Reveal the Inactivation of E. coli L-aspartate aminotransferase by (s)-4,5-dihydro-2thiophenecarboylic acid (SADTA) via two mechanisms (at pH 7.0).
Liu, D. (Contributor), Pozharski, E. (Contributor), Lepore, B. W. (Contributor), Fu, M. (Contributor), Silverman, R. B. (Contributor), Petsko, G. A. (Contributor) & Ringe, D. (Contributor), RCSB-PDB, 2007
DOI: 10.2210/pdb2qb2/pdb, https://www.rcsb.org/structure/2QB2
Dataset
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CCDC 227695: Experimental Crystal Structure Determination
Choi, S. (Creator) & Silverman, R. B. (Creator), Cambridge Crystallographic Data Centre, 2004
DOI: 10.5517/cc7my0s, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/cc7my0s&sid=DataCite
Dataset
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1P6N : Bovine endothelial NOS heme domain with L-N(omega)-nitroarginine-(4R)-amino-L-proline amide bound
Flinspach, M. L. (Contributor), Li, H. (Contributor), Jamal, J. (Contributor), Yang, W. (Contributor), Huang, H. (Contributor), Hah, J. (Contributor), Gómez-Vidal, J. A. (Contributor), Litzinger, E. A. (Contributor), Silverman, R. B. (Contributor) & Poulos, T. L. (Contributor), RCSB-PDB, 2004
DOI: 10.2210/pdb1p6n/pdb, https://www.rcsb.org/structure/1P6N
Dataset