91×ÔÅÄÂÛ̳

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 91×ÔÅÄÂÛ̳, 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.