Faculty

Research Overview

Dr. Ebetino has been involved in medicinal chemistry research for over 35 years. He has maintained a strong research interest in bisphosphonate drug design and new therapeutics for bone related diseases. He was part of the Procter & Gamble team that discovered and developed the drug Actonel® for osteoporosis and more recently established and led the Drug Discovery Department at Warner Chilcott Pharmaceuticals. His research and publications span a variety of therapeutic areas including Arthritis, Obesity, Infectious Diseases, Gastrointestinal Disease, and Cancer. Besides his continuing association with the University of Rochester, he has held several adjunct roles including Visiting Scholar at the University of Southern California, and is currently an Academic Visitor at the Structural Genomics Consortium, University of Oxford, UK and a Visiting Research Professor at Queen’s University, Belfast. He continues research efforts with collaborators internationally including the development of novel PET scanning probes and fluorescent diagnostic agents. A primary focus, particularly at the UR Chemistry Department, is his collaboration with Prof. Boeckman and the UR Medical School on bone targeted bisphosphonate conjugates of a variety of drug classes, including epigenetic enzyme inhibitors, proteosome inhibitors, and other heterocyclic therapeutics for the treatment of multiple myeloma, bone metastases, and arthritis.

Research Interests

• Medicinal chemistry and drug design, including bisphosphonates and bone targeted drugs for arthritis and cancer, receptor agonists/antagonists, and epigenetic enzyme inhibitors

Selected Publications

• Russell, R.G.G., Tsoumpra, M.K., Lawson, M., Chantry, A.D., Ebetino, F.H., Pazianas, M. "The Duration and Safety of Osteoporosis Treatment: Anabolic and Antiresorptive Therapy," Antiresorptives. Editors: Stuart Silverman and Bo Abrahamsen. Springer Publications. 2016, Chapter 2 pp. 17-36, In press ISBN: 978-3-319-23639-1 (Online).
• Sun S.T., Blazewska, K.M., Kashemirov, B.A., Duan X.C., Dunford, J.E., Russell R.G.G., Ebetino, F.H., McKenna C.E., et al. "Fluorescent bisphosphate and carboxyphosphate probes: A versatile toolkit for applications in bone biology and biomedicine," Bioconjugate Chemistry2015, {Epub ahead of print}.
• Tsoumpra, M.K., Muniz, J.R., Barnett, B.L., Kwaasi, A.A., Pilka, E.S., Kavanagh, K.L., Evdokimov, A., Walter, R.L., Von Delft, F., Ebetino, F.H., et al. "The inhibition of human farnesyl pyrophosphate synthase by nitrogen-containing bisphosphates. Elucidating the role of active site threonine 201 and tyrosine 204 residues using enzyme mutants," Bone2015, 81, 478-486.
• Misrah, J., Mohanty, S.T., Madan, S., Fernandes, J.A., Ebetino, F.H., Russell R.G.G., Bellantuono, l. "Zoledronate attenuates accumulation of DNA damage in mesenchymal stem cells and protects their function," Stem Cells2015, {Epub ahead of print}.
• Ebetino, F.H., Lundy, M.W., Kwaasi, A.A., Dunford, J., Duan, X., Triffitt, J., Mazur, A., Jeans, G., Barnett, B.L., Russell, R.G.G. "The Successful Design of a Novel Highly Potent Nitrogen-Containing Bisphosphate With Lower Bone Affinity," J. Bone and Min. Res.2013, 28(S1), 453-454.
• Moriceau, G., Roelofs, A.J., Brion, R., Redini, F., Ebetino, F.H., Rogers, M.J., Heymann, D. "Synergistic inhibitory effect of apomine and Iovastatin on osteosarcoma cell growth," Cancer2012, 118(3), 750-760.
• Ebetino, F.H., Hogan, A.-M.L., Sun, S., Tsoumpra, M.K., Duan, X., Triffitt, J.T., Kwaasi, A.A., Dunford, J.E., Barnett, B.L., Oppermann, U., Lundy, M.W., Boyde, A., Kashemirov, B.A., McKenna, C.E., Russell, R.G.G. "The Relationship Between the Chemistry and Biological Activity of the Bisphosphates," Bone2011, 49(1), 20-33.
• Blazewska, K.M., Ni, F., Haiges, R., Kashemirov, B.A., Coxon, F.P., Stewart, C.A., Baron, R., Rogers, M.J., Seabra, M.C., Ebetino, F.H., McKenna, C.E. "Synthesis, stereochemistry and SAR of a series of minodronate analogues as RGGT inhibitors," European Journal of Medicinal Chemistry2011, 46(10), 4820-4826.
• Tian, X., Switzer, A.G., Derose, S.A., Mishra, R.K., Solinsky, M.G., Mumin, R.N., Ebetino, F.H., Jayasinghe, L.R., Webster, M.E., Colson, A.O., Wos, J.A., et al. "Discovery of Orally Bioavailable 1,3,4-Trisubstituted 2-Oxopiperazine-Based Melanocortin-4 Receptor Agonists as Potential Antiobesity Agents," J. of Medicinal Chemistry2008, 51(19), 6055-6066.
• Ebetino, F.H., Roze, C.N., McKenna, C.E., Barnett, B.L., Dunford, J., Russell, R.G.G., Mieling, G., Rogers, M.J. "Molecular interaction of nitrogen-containing bisphosphates within farnesyl diphosphate synthase," Organometallic Chemistry2005, 690(10), 2679-2687.
• Ebetino, F.H., Soyke, E.G., Dansereau, S.M. "Bone Active Bisphosphonate Mechanistic Studies: Synthesis of a 2-Pyridinylmethylene Bisphosphonic Acid via a Photolytic Ring Contraction," Heteroatom Chem.2000, 11(0), 442-448.
• Schwan, T.J., Ebetino, F.H. "Nitrofurans," Concise Encyclopedia of Chemical Technology, 4th Edition Kirk-Othermer, Wiley Interscience. 1999, 81, 131.