Richard Bruce Silverman

Richard Bruce Silverman

Richard Silverman, Perkin Award, 2009
Born (1946-05-12)May 12, 1946 (age 70)
{Philadelphia, PA}
Residence U.S. [Winnetka, IL]
Nationality American
Fields Chemistry
Institutions Northwestern University
Alma mater Pennsylvania State University (B.S.)
Harvard University (Ph.D.)
Doctoral advisor David Dolphin
Known for Pregabalin (Lyrica)
Notable awards Perkin Medal (2009), Centenary Prize, Royal Society of Chemistry (2013), Excellence in Medicinal Chemistry Prize, Israel Chemical Society (2014)
External video
“Richard B. Silverman, Basic Science to Blockbuster Drug”, National Academy of Inventors

Richard Bruce Silverman (born May 12, 1946) is a chemistry professor at Northwestern University in the United States where he currently holds the title of Patrick G. Ryan/Aon Professor. His group's main focus is basic research into central nervous system disorders. He is the author of more than 350 research publications, 71 patents, and several books, including The organic chemistry of drug design and drug action, now in its third edition; the third edition was co-written by Mark H. Holladay.[1] He is best known for the discovery of pregabalin, which is marketed by Pfizer under the trade name Lyrica.[2]

Education

Silverman attended Central High School of Philadelphia, graduating in the 221st class.[3] Silverman received his B.S. in chemistry from Pennsylvania State University in 1968. He then spent a short time 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 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.[4]

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 as of 1986. He has held several named professorships. He was the Arthur Andersen Professor of Chemistry from 1996 to 1988, the Charles Deering McCormick Professor of Teaching Excellence from 2001 to 2003,[5] and the John Evans Professor of Chemistry beginning from 2004 to 2015.[6] He was named the Patrick G. Ryan/Aon Professor as of September 1, 2015.[4]

The primary focus in Silverman's laboratory is basic research into central nervous system disorders, including Parkinson’s disease, Huntington’s disease, cerebral palsy and epilepsy.[7] He has developed novel approaches to the elucidation of enzyme-catalyzed reactions in organic chemistry.[8] He is particularly interested in understanding and developing mechanisms of enzyme inhibition.[9] Silverman has published over 350 research articles.[5] He has been awarded at least 71 patents.[5] He has written at least 3 books: Mechanism-based enzyme inactivation: chemistry and enzymology (1988),[10] Organic chemistry of drug design and drug action (1992, 2004, 2014),[1] and Organic chemistry of enzyme-catalyzed reactions (2000, 2002).[11] He is active on the editorial boards of a number of scholarly journals.[8]

Silverman is best known for inventing the drug pregabalin as a possible treatment for epileptic seizures.[7] During 1988-1990, Ryszard Andruszkiewicz, a visiting research fellow, synthesized a series of molecules for Silverman.[12] One looked particularly promising.[13] The molecule was transported into the brain, where it activated the enzyme L-glutamate decarboxylase. Silverman hoped that the enzyme would increase production of the inhibitory neurotransmitter GABA and block convulsions.[7] 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.[7] It was approved by the FDA in 2004 and marketed by Pfizer (which bought out Parke-Davis) under the trade name Lyrica.[7][13]

Research has shown that the mechanism of the drug is more complicated than originally anticipated.[14] 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.[15][16]

Awards and honors

Memberships

Medals, Prizes

Teaching awards

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

In 1971 he received a U.S. Army Commendation Medal.

Philanthropy

Lyrica royalties paid to Northwestern, and a gift from Silverman himself, have supported the building of 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.[7][30]

References

  1. 1 2 Silverman, Richard B. (1992). The organic chemistry of drug design and drug action. San Diego: Acad. Press. ISBN 9780126437300.
  2. ↑ Francis, Theo (2007-08-17). "Health Blog: Lyrica Makes Rain at Northwestern". The Wall Street Journal. Retrieved 2008-04-17.
  3. ↑ "Dedication of the Silverman Faculty Lounge" (PDF). The Alumni Journal. Central High School of Philadelphia. 2014. Retrieved 20 May 2016.
  4. 1 2 "Curriculum Vitae". Retrieved 2008-04-17.
  5. 1 2 3 4 "iCON Innovator Award (University Level)". IBIO Institute. Retrieved 20 May 2016.
  6. 1 2 "Richard B. Silverman, Ph.D.". ACS Division of Medicinal Chemistry. Retrieved 19 May 2016.
  7. 1 2 3 4 5 6 Merrill, Nick (February 25, 2010). "Silverman's golden drug makes him NU's golden ticket". North by Northwestern. Retrieved 19 May 2016.
  8. 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 20 May 2016.
  9. ↑ Silverman, Richard B. (2009). "Mechanism-based enzyme inactivators". In Purich, Daniel L. Contemporary enzyme kinetics and mechanism. Amsterdam: Elsevier/Academic Press. pp. 331–. ISBN 9780123847447.
  10. ↑ Silverman, author, Richard B. (1988). Mechanism-based enzyme inactivation : chemistry and enzymology. Boca Raton, FL: CRC Press. ISBN 0849345421.
  11. ↑ Silverman, Richard B. (2000). The organic chemistry of enzyme-catalyzed reactions (Rev. ed.). San Diego, CA: Academic Press. ISBN 0126437459.
  12. ↑ Andruszkiewicz, R; Silverman, RB (25 December 1990). "4-Amino-3-alkylbutanoic acids as substrates for gamma-aminobutyric acid aminotransferase.". The Journal of biological chemistry. 265 (36): 22288–91. PMID 2266125.
  13. 1 2 Poros, Joanna (2005). "Polish scientist is the co-author of a new anti-epileptic drug". Science and Scholarship in Poland. Retrieved 19 May 2016.
  14. ↑ Silverman, Richard B. (28 April 2008). "From Basic Science to Blockbuster Drug: The Discovery of Lyrica". Angewandte Chemie International Edition. 47 (19): 3500–3504. doi:10.1002/anie.200704280. Retrieved 19 May 2016.
  15. ↑ 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.
  16. ↑ Lowe, Derek (March 25, 2008). "Getting To Lyrica". Science Translational Medicine.
  17. ↑ Fellman, Megan (October 29, 2014). "Three attend American Academy of Arts and Sciences ceremony". Northwestern News. Retrieved 19 May 2016.
  18. ↑ "American Academy of Arts and Sciences; 2014 FELLOWS AND THEIR AFFILIATIONS AT THE TIME OF ELECTION" (PDF).
  19. ↑ Fellman, Megan (December 17, 2014). "Three Professors Named National Academy of Inventors Fellows Inventors have demonstrated a "prolific spirit of innovation". Northwestern News. Retrieved 19 May 2016.
  20. ↑ "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. Retrieved 19 May 2016.
  21. ↑ "2014 MCS - ICS Award Letter" (PDF). T he Medicinal Chemistry Section of the ICS. April 10, 2014.
  22. ↑ "The ICS Barry Cohen Prize for medicinal chemistry". The Israel Chemical Society. Retrieved 20 May 2016.
  23. ↑ "Silverman Receives Trustee Medal for Faculty Innovation and Entrepreneurship". The Garage. Northwestern University. June 17, 2014. Retrieved 20 May 2016.
  24. 1 2 "Dr. Richard Silverman Awarded by American Chemical Society and Royal Society of Chemistry". Northwestern University. Retrieved 19 May 2016.
  25. ↑ "Centenary Prize 2013 Winner". Royal Society of Chemistry. Retrieved 19 May 2016.
  26. ↑ Silverman, Richard B. (26 January 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. Retrieved 20 May 2016.
  27. ↑ "Richard B Silverman, Creator of Lyrica, to Receive Perkin Medal". SCI America. Retrieved 19 May 2016.
  28. ↑ "Arthur C. Cope Scholar Awards". American Chemical Society. Retrieved 20 May 2016.
  29. ↑ "Past Fellows". Alfred P. Sloan Foundation. Retrieved 20 May 2016.
  30. ↑ "Northwestern University Richard and Barbara Silverman Hall for Molecular Therapeutics and Diagnostics". Thornton Tomasetti. Retrieved 19 May 2016.
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