Tony Taldone, PhD

Senior Research Scientist
Lab Phone:
646-888-2238

I am a trained medicinal chemist currently working in the laboratory of Dr. Gabriela Chiosis at Memorial Sloan Kettering Cancer Center as a research faculty. During the past five years I have been working to develop novel therapeutics targeting heat shock proteins, such as Hsp90, Hsp70 and Grp94, involved in cell stress and survival which may play a critical role in the development of cancer and potentially other diseases. We take a chemical biology approach to investigate heat shock proteins with the ultimate goal of translating agents into the clinic for the treatment of human diseases. In this regard, my expertise in designing and synthesizing small-molecule inhibitors as well as biological probes for these targets has been critical to the successful outcomes of our research projects. I have an extensive knowledge of chemistry and an understanding of its proper application for establishing structure activity relationships (SAR) as well as a keen understanding of what is required to transform a molecule into a drug. During the last five years I have also acquired knowledge of cancer biology and a belief that it is the biology which drives the successful development of any drug discovery program. I feel that my qualifications and experience to date put me in a position to uniquely impact the field and to potentially provide cures to cancer.

In an effort to better understand HSP tumor biology with the ultimate purpose of clinical translation of these agents, my research has focused on the design and synthesis of small-molecule inhibitors and chemical tools useful for detailed biological studies. Efforts thus far have even resulted in one agent, PU-H71, a potent inhibitor of Hsp90, to enter into clinical trials in patients with advanced solid tumors, lymphoma and myeloproliferative disorders. Furthermore, my direct association with the development of these clinical trials gave me a more profound understanding of the term “bench to bedside”. My research has also contributed towards the discovery and optimization of a novel class of small-molecule Hsp70 inhibitors which are currently undergoing evaluation for efficacy in pre-clinical models of cancer. To support these efforts, I have received two prestigious grants. During this period I have also been involved in a multitude of collaborative efforts. I have provided our collaborators with mg to gram amounts of small molecule inhibitors for which I have developed suitable scale-up synthetic methods, formulations for their proper in vivo use and have established conditions for their proper use and storage.

Publications by Tony Taldone

Selected Peer-reviewed Publications

  1. Lengyel, I., Cesare, V., Adam, I., Taldone, T. About four new trityl-substituted α-lactams. Heterocycles, 57(1), 73-95 (2002).
  2. Lengyel, I., Cesare, V., Chen, S., Taldone, T. About the factors which govern the ring-opening of α-lactams with benzylamine: I. The relative stability of the α-lactam and the substituent on nitrogen. Heterocycles, 57(4), 677-695 (2002).
  3. Lengyel, I., Cesare, V., Taldone, T. A direct link between the Passerini reaction and α-lactams.Tetrahedron, 60(5), 1107-1124 (2004).
  4. Taldone, T., Zito, S. W., Talele, T. T. Inhibition of dipeptidyl peptidase-IV (DPP-IV) by atorvastatin. Bioorganic and Medicinal Chemistry Letters, 18(2), 479-484 (2008).
  5. Taldone, T., Sun, W., Chiosis, G. Discovery and development of heat shock protein 90 inhibitors. Bioorganic and Medicinal Chemistry, 17(6), 2225-2235 (2009). PMCID: PMC2760286
  6. Caldas-Lopes, E., Cerchietti, L., Ahn, J. H., Clement, C. C., Robles, A. I., Rodina, A., Moulick, K., Taldone, T., Gozman, A., Guo, Y., Wu, N., de Stanchina, E., White, J., Gross, S. S., Ma, Y., Varticovski, L., Melnick, A., Chiosis G. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proceedings of the National Academy of Sciences, USA, 106(20), 8368-8373 (2009). PMCID: PMC2688867
  7. Taldone, T., Zatorska, D., Kang, Y., Chiosis, G. A facile and efficient synthesis of d6-labelled PU-H71, a purine scaffold Hsp90 inhibitor. Journal of Labelled Compounds and Radiopharmaceuticals, 53(1), 47-49 (2010).
  8. Taldone, T., Gillan, V., Sun, W., Rodina, A., Patel, P., Maitland, K., O’Neill, K., Chiosis, G., Devaney, E. Assay Strategies for the Discovery and Validation of Therapeutics Targeting Brugia pahangi Hsp90. PLoS Neglected Tropical Diseases, 4(6), e714 (2010).
  9. Taldone, T., Zatorska, D., Patel, P. D., Zong, H., Rodina, A., Ahn, J. H., Moulick, K., Guzman, M. L., Chiosis, G. Design, synthesis, and evaluation of small molecule Hsp90 probes. Bioorganic and Medicinal Chemistry, 19(8), 2603–2614 (2011). PMCID: PMC3143825
  10. Taldone, T., Gomes-DaGama, E. M., Zong, H., Sen, S., Alpaugh, M. L., Zatorska, D., Alonso-Sabadell, R., Guzman, M. L., Chiosis, G. Synthesis of purine-scaffold fluorescent probes for heat shock protein 90 with use in flow cytometry and fluorescence microscopy. Bioorganic and Medicinal Chemistry Letters, 21(18), 5347-5352 (2011). PMCID: PMC3175602
  11. Moulick, K., Ahn, J. H., Zong, H., Rodina, A., Cerchietti, L., Gomes, DaGama, E. M., Caldas-Lopes, E., Beebe, K., Perna, F., Hatzi, K., Vu, L. P., Zhao, X., Zatorska, D., Taldone, T., Smith-Jones, P., Alpaugh, M., Gross, S. S., Pillarsetty, N., Ku, T., Lewis, J. S., Larson, S. M., Levine, R., Erdjument-Bromage, H., Guzman, M. L., Nimer, S. D., Melnick, A., Neckers, L., Chiosis, G. Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90. Nature Chemical Biology, 7(11), 818-826 (2011). PMCID: PMC3265389
  12. Taldone, T., Zatorska, D., Chiosis, G. Reaction of 2-Naphthylamine with Sodium Iodate/Sodium Sulfite:Synthesis of 2-Amino-1-iodonaphthalene. Synthetic Communications, 42(5), 635-638 (2012).
  13. Taldone, T., Patel, P. D., Patel, H. J., Chiosis, G. About the reaction of aryl fluorides with sodium sulfide: investigation into the selectivity of substitution of fluorobenzonitriles to yield mercaptobenzonitriles via SNAr displacement of fluorine. Tetrahedron Letters, 53(20), 2548-2551 (2012).
  14. Taldone T, Patel PD, Patel M, Patel HJ, Evans CE, Rodina A, Ochiana S, Shah SK, Uddin M, Gewirth DT, Chiosis G. Experimental and structural testing module to analyze paralog-specificity and affinity in the Hsp90 inhibitors series. J. Med. Chem 2013 DOI: 10.1021/jm400619b, August 21, 2013
  15. Pallav D. Patel, Pengrong Yan, Paul M. Seidler, Hardik J. Patel, Weilin Sun, Chenghua Yang, Nanette S. Que, Tony Taldone, Paola Finotti, Ralph A. Stephani, Daniel T. Gewirth, Gabriela Chiosis. Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2. Nature Chemical Biology 2013 doi: 10.01038/nchembio.1335, September 1, 2013.

Patents

  1. Chiosis, Gabriela; Taldone, T.; Rodina, A.; Patel, P.; Kang, Y., Heat Shock Protein Binding Compounds, Compositions, and Methods for Making and Using Same, Memorial Sloan Kettering Cancer Center,  WO2011022440, February 24, 2011.
  2. Chiosis, Gabriela; Taldone, T.; Sun, W., Purine Derivatives Useful as HSP90 Inhibitors, Memorial Sloan Kettering Cancer Center, WO2011044394, April 14, 2011.
  3. Chiosis, Sun, Taldone, Patel, SK2011‐011‐02 Hsp90 inhibitors: Priority Filing Number 61/472,061; Priority Date Apr 5, 2011; Application Number PCT/US12/32371 Application Date Apr 5, 2012
  4. Chiosis, Sun, Taldone, Patel, SK2011‐011‐03 Hsp90 Inhibitors; Priority Filing Number 61/472,061 Priority Date Apr 5, 2011 Application Number PCT/US12/32373 Application Date Apr 5, 2012
  5. Gomes‐DaGama, Chiosis, Lewis, Alpaugh, Pillarsetty, Larson, Taldone SK2011‐035‐02: Priority Filing Number 61/506,010, Priority Date Jul 8, 2011, Application Number PCT/US2012/045861, Application Date Jul 6, 2012
  6. Gabriela Chiosis, Tony Taldone, Anna Rodina, Pallav Patel, Yanlong Kang: Heat shock protein binding compounds, compositions, and methods for making and using same. Memorial Sloan Kettering Cancer Center. Oct, 4 2012: US20120252818
  7. Gabriela Chiosis, Tony Taldone, Pallav Patel, Hardik Patel, Weilin Sun, Pengrong Yan, Chenghua Yan: Selective Grp94 inhibitors and uses thereof. Memorial Sloan Kettering Cancer Center.  2013