Richard Bruce Silverman
Richard Silverman, Perkin Award, 2009
Born (1946-05-12) May 12, 1946
Philadelphia, PA
NationalityAmerican
Alma materPennsylvania State University (B.S.)
Harvard University (Ph.D.)
Known forPregabalin (brand name Lyrica)
AwardsPerkin Medal (2009), Centenary Prize, Royal Society of Chemistry (2013), Excellence in Medicinal Chemistry Prize, Israel Chemical Society (2014), Award for Creative Invention of the American Chemical Society (2017), Tetrahedron Prize for Creativity in Organic Chemistry (2021), Elected member, National Academy of Sciences (2023)
Scientific career
FieldsChemistry
InstitutionsNorthwestern University
Doctoral advisorDavid Dolphin
External videos
video icon "Richard B. Silverman, Basic Science to Blockbuster Drug", National Academy of Inventors

Richard Bruce Silverman (born May 12, 1946) is the Patrick G. Ryan/Aon Professor of Chemistry at Northwestern University. His group's main focus is basic and translational research into central nervous system disorders and cancer. He is known for the discovery of pregabalin, which is marketed by Pfizer under the brand name Lyrica.[1]

Education

Silverman attended Central High School of Philadelphia.[2] Silverman received his B.S. in chemistry from Pennsylvania State University in 1968. He spent one semester at Harvard University before being drafted and serving as a United States Army Physical Sciences Assistant at the Walter Reed Army Institute of Research from January 1969 until his honorable discharge in January 1971. In June 1974, he received his Ph.D. from Harvard University in organic chemistry with advisor David Dolphin. He then spent two years as a postdoctoral fellow with Robert Abeles in biochemistry at Brandeis University.[3]

Research

Silverman has been teaching and doing research at Northwestern since 1976. He became both professor of chemistry and professor of biochemistry, molecular biology, and cell biology in 1986. He has held several named professorships. He was the Arthur Andersen Professor of Chemistry from 1988 to 1996, the Charles Deering McCormick Professor of Teaching Excellence from 2001 to 2003,[4] and the John Evans Professor of Chemistry beginning from 2004 to 2015.[5] He was named the inaugural Patrick G. Ryan/Aon Professor as of September 1, 2015.[3]

The primary focus in Silverman's laboratory is basic research into central nervous system disorders, including Amyotrophic lateral sclerosis (ALS), Parkinson's disease, Alzheimer's disease, and epilepsy.[6] Other research areas include cancer (melanoma and hepatocellular carcinoma). He has developed novel approaches to the elucidation of enzyme-catalyzed reactions in organic chemistry.[7] He is interested in understanding and developing mechanisms of enzyme inhibition.[8]

Silverman has published about 400 research articles. He has been awarded 130 patents. He has written 3 books (one in the third edition): Mechanism-Based Enzyme Inactivation: Chemistry and Enzymology (CRC Press; 1988), Organic Chemistry of Drug Design and Drug Action (Academic Press; 1992, 2004, 2014), and Organic Chemistry of Enzyme-Catalyzed Reactions (Academic Press; 2000, 2002; see the Published works section, below). He is active on the editorial boards of a number of scholarly journals.[7]

Silverman is known for inventing the drug pregabalin as a possible treatment for epileptic seizures.[6] During 1988-1990, Ryszard Andruszkiewicz, a visiting research fellow, synthesized a series of molecules for Silverman.[9] One looked promising.[10] The molecule was transported into the brain, where it activated the enzyme L-glutamate decarboxylase. Silverman anticipated that the enzyme would increase production of the inhibitory neurotransmitter GABA and block convulsions.[6] Eventually, the set of molecules were sent to Parke-Davis Pharmaceuticals for testing. In addition to treating seizures, pregabalin was found to be effective in treating fibromyalgia pain, neuropathic pain, and generalized anxiety disorder.[6] It was approved by the FDA in 2004 and marketed by Pfizer (which bought Parke-Davis) under the trade name Lyrica.[6][10]

Research has shown that the mechanism of the drug is more complicated than originally anticipated.[11] In addition to its effects on GABA-AT substrate behavior, pregabalin binds to calcium channels and blocks glutamate release. GABA is potentiated, but through a different mechanism than originally suspected.[12][13]

Awards and honors

Memberships

Medals, Prizes

Teaching awards

Silverman has received numerous teaching awards from Northwestern University, including the following:

  • 2001-2004 Charles Deering McCormick Professor of Teaching Excellence
  • 2000 Alumni Association Excellence in Teaching Award
  • 1999 Excellence in Chemistry Education Award from the Northwestern University chapter of Alpha Chi Sigma Chemistry Fraternity
  • 1999 E. LeRoy Hall Award for Teaching Excellence

Philanthropy

Lyrica royalties paid to Northwestern, and a gift from Silverman himself, have supported the Silverman Hall for Molecular Therapeutics and Diagnostics at Northwestern University. Silverman Hall, which opened in 2009, was designed to be a collaborative and interdisciplinary facility housing researchers from chemistry, biology, and engineering.[6][27]

Published works

Books

  • Silverman, Richard B. (1988) [1988]. Mechanism-Based Enzyme Inactivation: Chemistry and Enzymology (1st ed.). Boca Raton, Fl.: CRC Press. ISBN 978-0849345432. Retrieved February 5, 2022.

References

  1. ↑ Francis, Theo (August 17, 2007). "Health Blog: Lyrica Makes Rain at Northwestern". The Wall Street Journal. Retrieved April 17, 2008.
  2. ↑ "Dedication of the Silverman Faculty Lounge" (PDF). The Alumni Journal. Central High School of Philadelphia. 2014. Retrieved May 20, 2016.
  3. 1 2 "Curriculum Vitae". Archived from the original on May 15, 2008. Retrieved April 17, 2008.
  4. 1 2 "iCON Innovator Award (University Level)". IBIO Institute. Retrieved May 20, 2016.
  5. 1 2 "Richard B. Silverman, Ph.D." ACS Division of Medicinal Chemistry. Retrieved May 19, 2016.
  6. 1 2 3 4 5 6 Merrill, Nick (February 25, 2010). "Silverman's golden drug makes him NU's golden ticket". North by Northwestern. Archived from the original on June 1, 2016. Retrieved May 19, 2016.
  7. 1 2 3 Wessner, Charles W. (2013). Building the Illinois innovation economy. summary of a symposium. Washington, D.C.: National Academies Press. pp. 172–173. ISBN 978-0-309-27869-0. Retrieved May 20, 2016.
  8. ↑ Silverman, Richard B. (2009). "Mechanism-based enzyme inactivators". In Purich, Daniel L. (ed.). Contemporary enzyme kinetics and mechanism. Amsterdam: Elsevier/Academic Press. pp. 331–. ISBN 9780123847447.
  9. ↑ Andruszkiewicz, R; Silverman, RB (December 25, 1990). "4-Amino-3-alkylbutanoic acids as substrates for gamma-aminobutyric acid aminotransferase". The Journal of Biological Chemistry. 265 (36): 22288–91. doi:10.1016/S0021-9258(18)45702-X. PMID 2266125.
  10. 1 2 Poros, Joanna (2005). "Polish scientist is the co-author of a new anti-epileptic drug". Science and Scholarship in Poland. Archived from the original on August 20, 2016. Retrieved May 19, 2016.
  11. ↑ Silverman, Richard B. (April 28, 2008). "From Basic Science to Blockbuster Drug: The Discovery of Lyrica". Angewandte Chemie International Edition. 47 (19): 3500–3504. doi:10.1002/anie.200704280. PMID 18307181.
  12. ↑ Taylor, CP; Angelotti, T; Fauman, E (February 2007). "Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery". Epilepsy Research. 73 (2): 137–50. doi:10.1016/j.eplepsyres.2006.09.008. PMID 17126531. S2CID 54254671.
  13. ↑ Lowe, Derek (March 25, 2008). "Getting To Lyrica". Science Translational Medicine.
  14. ↑ Fellman, Megan (October 29, 2014). "Three attend American Academy of Arts and Sciences ceremony". Northwestern News. Retrieved May 19, 2016.
  15. ↑ "American Academy of Arts and Sciences; 2014 FELLOWS AND THEIR AFFILIATIONS AT THE TIME OF ELECTION" (PDF).
  16. ↑ Fellman, Megan (December 17, 2014). "Three Professors Named National Academy of Inventors Fellows Inventors have demonstrated a "prolific spirit of innovation". Northwestern News. Retrieved May 19, 2016.
  17. ↑ "2011 ACS Fellows Society honors 213 members in the third year of its fellows program". Chemical & Engineering News. 89 (32): 58–60. August 8, 2011. doi:10.1021/cen-v089n032.p058. Retrieved May 19, 2016.
  18. ↑ "2014 MCS - ICS Award Letter" (PDF). T he Medicinal Chemistry Section of the ICS. April 10, 2014.
  19. ↑ "The ICS Barry Cohen Prize for medicinal chemistry". The Israel Chemical Society. Retrieved May 20, 2016.
  20. ↑ "Silverman Receives Trustee Medal for Faculty Innovation and Entrepreneurship". The Garage. Northwestern University. June 17, 2014. Retrieved May 20, 2016.
  21. 1 2 "Dr. Richard Silverman Awarded by American Chemical Society and Royal Society of Chemistry". Northwestern University. Retrieved May 19, 2016.
  22. ↑ "Centenary Prize 2013 Winner". Royal Society of Chemistry. Retrieved May 19, 2016.
  23. ↑ Silverman, Richard B. (January 26, 2012). "The 2011 E. B. Hershberg Award for Important Discoveries in Medicinally Active Substances: (1,3)-3-Amino-4-difluoromethylenyl-1-cyclopentanoic Acid (CPP-115), a GABA Aminotransferase Inactivator and New Treatment for Drug Addiction and Infantile Spasms". Journal of Medicinal Chemistry. 55 (2): 567–575. doi:10.1021/jm201650r. PMC 3266980. PMID 22168767.
  24. ↑ "Richard B Silverman, Creator of Lyrica, to Receive Perkin Medal". SCI America. Retrieved May 19, 2016.
  25. ↑ "Arthur C. Cope Scholar Awards". American Chemical Society. Retrieved May 20, 2016.
  26. ↑ "Past Fellows". Alfred P. Sloan Foundation. Archived from the original on November 6, 2016. Retrieved May 20, 2016.
  27. ↑ "Northwestern University Richard and Barbara Silverman Hall for Molecular Therapeutics and Diagnostics". Thornton Tomasetti. Retrieved May 19, 2016.
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