Dr Jeffrey Bruce Smaill

BSc(Hons), PhD

Biography

Jeff Smaill obtained his BSc(Hons) and PhD degrees in the field of synthetic organic chemistry from the University of Otago in the laboratory of Professor Peter K Grant. He then completed a postdoctoral fellowship at the University of Cambridge under the supervision of Professor Ian Paterson, developing a biomimetic approach to the total synthesis of the polyether antibiotic Etheromycin. He joined the Auckland Cancer Society Research Centre in 1994 and has been involved in drug development collaborations with Circadian Pharmaceuticals and Pfizer Global Research and Development. He is currently an Associate Investigator of the Maurice Wilkins Centre for Molecular Biodiscovery, a Project Leader on a New Economy Research Fund Programme Grant, a Co-Principle Investigator on a Health Research Council Project Grant and a Named Investigator on a Health Research Council Programme Grant. He is active in a number of medicinal chemistry related research projects.

Dr Smaill has extensive experience in the design and synthesis of ATP-competitive small molecule kinase inhibitors. He has been involved in the elucidation of structure-activity relationships for 4-anilinoquinazolines and 4-anilinopyridopyrimidines as irreversible inhibitors of the Human Epidermal Growth Factor Receptor (HER) family. Culminating in the development of CI-1033 (canertinib dihydrochloride), the first irreversible inhibitor of HER1-4 to enter clinical trials. He has published on 2-anilino-6-phenylpyrido[2,3-d]pyrimidin-7(8H)-ones and 4-phenylpyrrolocarbazoles as inhibitors of the cell-cycle checkpoint control protein Wee1 and N-phenylbenzimidazoles as inhibitors of the Platelet Derived Growth Factor Receptor (PDGFR). He is currently interested in developing the next generation of bioreductive prodrugs with a focus on using a hypoxia-activated prodrug strategy to impart increased tumour-selectivity to novel multikinase inhibitors.

Research interests

Selected publications and creative works (Research Outputs)

  • Li, X., Guise, C. P., Taghipouran, R., Yosaatmadja, Y., Ashoorzadeh, A., Paik, W.-K., ... Xu, Y. (2017). 2-Oxo-3, 4-dihydropyrimido[4, 5-d]pyrimidinyl derivatives as new irreversible pan fibroblast growth factor receptor (FGFR) inhibitors. European journal of medicinal chemistry, 135, 531-543. 10.1016/j.ejmech.2017.04.049
    Other University of Auckland co-authors: Christopher Guise, Christopher Squire, Adam Patterson, Amir Ashoorzadeh, Yuliana Yosaatmadja
  • Zygouropoulou, M., Kubiak, A. M., Copp, J. N., Dubois, L. J., Mowday, A. M., Guise, C. P., ... Patterson, A. V. (2017). Clostridium as "Trojan Horse" Vectors for Cancer Treatment. Paper presented at 20th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), Washington, DC. 10 May - 13 May 2017. MOLECULAR THERAPY. (pp. 1).
    Other University of Auckland co-authors: Christopher Guise, Adam Patterson
  • Mowday, A. M., Guise, C. P., Kubiak, A. M., Minton, N. P., Abbattista, M. R., Lambin, P., ... Patterson, A. V. (2017). Efficacy of a Novel Enzyme/Prodrug Combination for Clostridia Directed Enzyme Prodrug Therapy. Paper presented at 20th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), Washington, DC. 10 May - 13 May 2017. MOLECULAR THERAPY. (pp. 2).
    Other University of Auckland co-authors: Christopher Guise, Adam Patterson
  • Mo, C., Zhang, Z., Guise, C. P., Li, X., Luo, J., Tu, Z., ... Ren, X. (2017). 2-Aminopyrimidine Derivatives as New Selective Fibroblast Growth Factor Receptor 4 (FGFR4) Inhibitors. ACS Medicinal Chemistry Letters, 8 (5), 543-548. 10.1021/acsmedchemlett.7b00091
    Other University of Auckland co-authors: Christopher Guise, Adam Patterson
  • Copp, J. N., Mowday, A. M., Williams, E. M., Guise, C. P., Ashoorzadeh, A., Sharrock, A. V., ... Ackerley, D. F. (2017). Engineering a Multifunctional Nitroreductase for Improved Activation of Prodrugs and PET Probes for Cancer Gene Therapy. Cell chemical biology, 24 (3), 391-403. 10.1016/j.chembiol.2017.02.005
    Other University of Auckland co-authors: Christopher Guise, Amir Ashoorzadeh, Jack Flanagan, Adam Patterson, Alexandra Mowday
  • Smaill, J. B., Gonzales, A. J., Spicer, J. A., Lee, H., Reed, J. E., Sexton, K., ... Blaser, A. (2016). Tyrosine Kinase Inhibitors. 20. Optimization of Substituted Quinazoline and Pyrido[3,4- d ]pyrimidine Derivatives as Orally Active, Irreversible Inhibitors of the Epidermal Growth Factor Receptor Family. Journal of Medicinal Chemistry, 59 (17), 8103-8124. 10.1021/acs.jmedchem.6b00883
    URL: http://hdl.handle.net/2292/32487
    Other University of Auckland co-authors: Bill Denny, Andrew Thompson, Julie Spicer, Brian Palmer, Adrian Blaser
  • Mowday, A. M., Ashoorzadeh, A., Williams, E. M., Copp, J. N., Silva, S., Bull, M. R., ... Guise, C. P. (2016). Rational design of an AKR1C3-resistant analog of PR-104 for enzyme-prodrug therapy. Biochemical pharmacology, 116, 176-187. 10.1016/j.bcp.2016.07.015
    URL: http://hdl.handle.net/2292/30209
    Other University of Auckland co-authors: Alexandra Mowday, Jack Flanagan, Adam Patterson, Bob Anderson, Christopher Guise, Maria Abbattista, Amir Ashoorzadeh, Matthew Bull
  • Patterson, A. V., Kimple, R. J., Jackson, V. J., Swick, A. D., Guise, C. P., Abbattista, M. R., ... Sun, J. D. (2016). Development of biomarkers to guide the clinical development of tarloxotinib bromide, a hypoxia-activated irreversible EGFR/HER2 inhibitor.. Paper presented at Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Chicago, IL. 2 June - 6 June 2017. JOURNAL OF CLINICAL ONCOLOGY. (pp. 3). 10.1200/JCO.2016.34.15_suppl.e17521
    Other University of Auckland co-authors: Adam Patterson, Christopher Guise, Matthew Bull

Contact details

Primary location

M&HS BUILDING 504 - Bldg 504
Level 1, Room 120
85 PARK RD
GRAFTON
AUCKLAND 1023
New Zealand