Philip Portoghese, PhD

Distinguished Professor, Department of Medicinal Chemistry

Philip Portoghese

Contact Info

porto001@umn.edu

Office Phone 612-624-9174

Fax 612-626-3114

Office Address:
8-111 Weaver-Densford Hall

Mailing Address:
University of Minnesota
College of Pharmacy
Department of Medicinal Chemistry
8-101 Weaver-Densford Hall
308 Harvard St. SE
Minneapolis, MN 55455

Lab Address:
8-115 Weaver-Densford Hall

PhD, Medicinal Chemistry, University of Wisconsin, 1961

M.S., Columbia University

Bachelor's, Columbia University, 1953

Summary

1961 – 1964 University of Minnesota: Assistant Professor of Medicinal Chemistry 
1964 – 1969 University of Minnesota: Associate Professor of Medicinal Chemistry 
1969 – 2000 University of Minnesota: Professor of Medicinal Chemistry 
1972 – 2011 Editor-in-Chief, Journal of Medicinal Chemistry, American Chemical Society
1974 – 1986 University of Minnesota: Director of Graduate Studies in Medicinal Chemistry 
1974 – 1983 University of Minnesota: Head of Medicinal Chemistry Department 
1987 – present University of Minnesota: Professor of Pharmacology 
2000 – present University of Minnesota: Distinguished Professor of Medicinal Chemistry

Expertise

Prof Portoghese's research focus has been in the area of opioids and opioid receptors. Concurrent with his research activities, he has served as Editor-in-Chief of the Journal of Medicinal Chemistry (1972-2011) for the American Chemical Society. With graduate faculty appointments in Pharmacology and Neuroscience in addition to his home Department, he has ongoing research collaborations in these departments and elsewhere at the University of Minnesota Academic Health Center. Some of the major contributions of Prof Portoghese's research group have been based on the development of concepts that relate to the interaction of opioid ligands with opioid receptors. The multiple modality concept based on the structure-activity relationships of opioid ligands led to the proposal of multiple opioid receptors (1965), which at that time was a departure from the prevailing view of a single receptor type. His group developed selective opioid antagonists such a BFNA (u), nor-BNI (k), and naltrindole (o) that presently are standards for the three opioid receptor types employed in opioid research. His initial studies with bivalent ligands that contain two mu opioid pharmacophores, led to the first propose mu opioid receptor dimers (1982). With the first report (1999) opioid receptor heterodimers (heteromer) by others, Prof Poroghese's research veered to the design of ligands that recognize opioid receptor heteromers, that is the theme of his current research. In this regard, his group has focused on bivalent ligands as agents to study or treat pain associated with neuropathy. This approach has led to the recent development of bivalent ligands (MMG22, MCC22) that produce profound antinociception (fmol ED50 range) without tolerance in the treatment of neuropathic pain. 

Awards & Recognition

  • 1973 – 1974 Gustavus A. Pfeiffer Fellow, American Pharmaceutical Association 
  • 1980 Research Achievement Award in Medicinal Chemistry, APhA Academy of Pharm. Sci. 
  • 1984 Ernest H. Volweiler Award for Outstanding Contributions to Research in the Pharmaceutical Sciences, American Association of Colleges of Pharmacy 
  • 1986 Honorary Doctorate, University of Catania, Italy 
  • 1990 Medicinal Chemistry Award, Division of Medicinal Chemistry, ACS. 
  • 1990 Research Achievement Award in Medicinal Chemistry, American Association of Pharmaceutical Scientists 
  • 1991 Nathan B. Eddy Award for Excellence in Drug Abuse Research, College on Problems of Drug Dependence 
  • 1991 Edward E. Smissman-Bristol-Myers-Squibb Award, Medicinal Chemistry Division, ACS
  • 1992 Honorary Doctorate, Royal Danish School of Pharmacy, Copenhagen 
  • 1996 Citation of Merit, University of Wisconsin 
  • 1997 – 2006 MERIT Award (Method to Extend Research In Time) National Institutes of Health
  • 1999 Pharmacy Honor Society Award, Rho Chi
  • 1999 The Oak & the Tulip Medal, presented by the sponsors of the Camerino-Nordwijkerhout Symposium, The Italian Chemical Society, and the European Federation of Medicinal Chemistry 
  • 2000 Alfred Burger Award in Medicinal Chemistry, American Chemical Society 
  • 2000 Distinguished Professor, University of Minnesota 
  • 2000 Citation of Excellence in Teaching, Research, and Service, University of Minnesota 
  • 2001 Weaver Medal, College of Pharmacy, University of Minnesota, 
  • 2001 Institute of Scientific Information, "one of the most cited, influencential researchers" in his field
  • 2003 Academy for Excellence in Health Research, Academic Health Center, University of Minnesota
  • 2006 Nauta Award in Pharmacochemistry, European Federation of Medicinal Chemistry 
  • 2007 Member, Medicinal Chemistry Hall of Fame, Div. of Medicinal Chemistry, American Chemical Society
  • 2015 Takeru Higuchi Research Prize, Academy of Pharmaceutical Sciences, American Pharmaceutical Association

AWARDS PRESENTED BY UNIVERSITIES AND INSTITUTES:

  • Honorary Doctorate, University of Catania, Italy, 1986
  • Honorary Doctorate, Royal Danish School of Pharmacy, Copenhagen, Denmark, 1992
  • Citation of Merit, University of Wisconsin, 1996
  • MERIT (Method to Extend Research In Time) Award, National Institutes of Health, 1997-2007
  • Citation of Excellence in Teaching, Research and Service, University of Minnesota, 2000
  • Distinguished Professor, College of Pharmacy, University of Minnesota, 2000-present
  • Member, Highly Cited Researchers database, Institute for Scientific Information
  • Weaver Medal, University of Minnesota, College of Pharmacy, 2001
  • Academy for Excellence in Health Research, Academic Health Center, University of Minnesota, 2003

AWARDS PRESENTED BY SCIENTIFIC AND PROFESSIONAL SOCIETIES:

  • Takeru Higuchi Research Prize, presented by the American Pharmaceutical Association, Academy of Pharmaceutical Sciences, 2015.
  • The American Chemical Society established an award in 2010, The “P.S. Portoghese Lectureship”, presented annually by an outstanding researcher at a national ACS meeting.
  • Member, Medicinal Chemistry Hall of Fame, Division of Medicinal Chemistry, American Chemical Society, 2007
  • Nauta Award in Pharmacochemistry, presented by the European Federation of Medicinal Chemistry, 2006
  • Alfred Burger Award in Medicinal Chemistry, presented by the American Chemical Society, 2000
  • The Oak & the Tulip Medal, presented by the sponsors of the Camerino-Nordwijkerhout Symposium, The Italian Chemical Society, and the European Federation of Medicinal Chemistry, 1999
  • Rho Chi Pharmacy Honor Society Award, 1999
  • Edward E. Smissman-Bristol-Myers-Squibb Award, presented by the Division of Medicinal Chemistry, American Chemical Society, 1991
  • Nathan B. Eddy Award For Excellence in Drug Abuse Research, presented by the College on Problems of Drug Dependence, NAS-NRC, 1991
  • Research Achievement Award in Medicinal Chemistry, presented by the American Association of Pharmaceutical Scientists, 1990
  • Medicinal Chemistry Award, presented by the Division of Medicinal Chemistry, American Chemical Society, 1990
  • Ernest H. Volwiler Award for Outstanding Contributions to Research in the Pharmaceutical Sciences, presented by the American Association of Colleges of Pharmacy, 1984
  • Research Achievement Award in Medicinal Chemistry, presented by the American Pharmaceutical Association/Academy of Pharmaceutical Sciences, 1980
  • Gustavus A. Pfeiffer Fellow, American Pharmaceutical Association, 1973-74

Professional Associations

American Chemical Society 

Research

Research Summary/Interests

Prof. Portoghese’s laboratory is focused on the design and synthesis of compounds that target opioid receptors, both as pharmacologic tools and as agents for treatment of pain. Novel concepts and approaches are employed for development of analgesics that are highly selective for different types of opioid receptors. These studies have utilized animal studies, cloned receptors and molecular modeling as an aid to obtain insight into the recognition of ligands by opioid receptors.

Patents

  • Selective Analgesic Agents,” P.S. Portoghese and R.M. Jones, US 2005-0004039-A1, Jan 6, 2005.
  • Therapeutic Compounds and Methods, P.S. Portoghese, R.M. Jones, and S.K. Sharma. US 7,232,829 B2, June 19, 2007.
  • Analgesic Conjugates, P.S. Portoghese and S.C. Roerig, US 2009/0233841 A1, Sept 17, 2009
  • Analgesic Agents, P.S. Portoghese and Ajay S. Yekkirala, US 8609682 B2, Dec. 17, 2013.
  • Compositions and methods of treating opioid addiction, P.R. Pentel, P.S. Portoghese, M. Pravatoni, and M.C.P. Le Naour, US 2014/0093525, April 3, 2014.

Publications

  • M. D. Metcalf, A. S. Yekkirala, M.D. Powers, K. F Kitto, C.A. Fairbanks, G.L. Wilcox, P.S. Portoghese, The ? Opioid Receptor Agonist SNC80 Selectively Activates Heteromeric ?-? Opioid Receptors. ACS Chem. Neurosci. 3, 505-509 (2012)
  • Yekkirala, Ajay S.; Banks, Matthew L.; Lunzer, Mary M.; Negus, Stevens S.; Rice, Kenner C.; Portoghese, Philip S. Clinically Employed Opioid Analgesics Produce Antinociception via ?-? Opioid Receptor Heteromers in Rhesus Monkeys. ACS Chem. Neurosci. 3,720-727. (2012).
  • Yekkirala, Ajay S.; Kalyuzhny, Alexander E.; Portoghese, Philip S. An immunocytochemical-derived correlate for evaluating the bridging of heteromeric mu-delta opioid protomers by bivalent ligands. ACS Chem. Biol. 8, 1412-1416 (2013).
  • Le Naour, Morgan; Akgun, Eyup; Yekkirala, Ajay; Lunzer, Mary M.; Powers, Mike D.; Kalyuzhny, Alexander E.; Portoghese, Philip S. Bivalent Ligands That Target ? Opioid (MOP) and Cannabinoid1 (CB1) Receptors Are Potent Analgesics Devoid of Tolerance. J. Med. Chem. 56, 5505-5513 (2013),
  • Pravetoni, M. Le Naour, T. M. Harmon, A. M. Tucker, P. S. Portoghese, P. R. Pentel, Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats. Vaccine, in press, (2013).
  • Marco Pravetoni,Morgan Le Naour, Ashli M. Tucker, Theresa M. Harmon, Tara M. Hawley, Philip S. Portoghese,and Paul R. Pentel,Reduced Antinociception of Opioids in Rats and Mice by Vaccination with Immunogens Containing Oxycodone and HydrocodoneHaptens, J. Med. Chem. 56, 915-923 (2013).
  • Akgun, E.; Javed, M.I.; Lunzer, M.M.; Smeester, B.A.; Beitz, A.J. Portoghese, P.S.Ligands that interact with putative MOR-mGluR5 heteromer produce potent antinociception in mice with inflammatory pain. Proc. Nat Acad Sci. USA, 110, 11595 – 11599 (2013).
  • Le Naour, Morgan; Lunzer, Mary M.; Powers, Michael D.; Kalyuzhny, Alexander E.; Benneyworth, Michael A.; Thomas, Mark J.; Portoghese, Philip S. Putative Kappa Opioid Heteromers As Targets for Developing Analgesics Free of Adverse Effects.J. Med. Chem. 57, 6383-6392 (2014).
  • Smeester, B.A.; Lunzer, M.M; Akgün E.; BeitzA. J.; Portoghese, P.S. Targeting putative mu opioid/metabotropic glutamate receptor-5 heteromers produces potent antinociception in a chronic murine bone cancer model. Eur. J. Pharmacol. 743, 48-52 (2014).
  • Akgün E, Javed MI, Lunzer MM, Powers MD, Sham YY, Watanabe Y, Portoghese PS.Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR5). J. Med. Chem. 58, 8647-57 (2015).