Dr Jeffrey Bruce Smaill

BSc(Hons), PhD

Biography

I obtained my 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. I 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. I am currently a Associate Professor at the Auckland Cancer Society Research Centre in the Faculty of Medical and Health Sciences at the University of Auckland. I have been the Principal Investigator of several large public good health research grants including prestigious grants from the Health Research Council of New Zealand, the US National Institutes of Health and the European Research Council. I am also a Associate Investigator of the Maurice Wilkins Centre for Molecular Biodiscovery, one of New Zealand’s ten Centres of Research Excellence. I have had 25 years of experience leading drug discovery programmes in collaboration with University start-up companies, small to medium sized biotechnology companies and large pharmaceutical companies. I have acted as a paid scientific consultant for Proacta Incorporated, Threshold Pharmaceuticals and Convert Pharmaceuticals. I am currently a member of the Scientific Advisory Board of Rain Therapeutics. In 2018, I won the Vice Chancellor’s Commercialisation Medal, the University of Auckland’s highest research award.

I have extensive experience in the design and synthesis of ATP-competitive small molecule kinase inhibitors. I have 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. My research in collaboration with Pfizer Global Research and Development has included the discovery of canertinib, the first irreversible kinase inhibitor to enter clinical trial. Further collaboration with Pfizer lead to the discovery of dacomitinib, a leading second generation irreversible EGFR/HER2 inhibitor that has successfully completed phase III trial and is expected to gain global approval in 2018. I have published on structure-based design of inhibitors targeted at EGFR, HER2, FGFR, PDGFR, WEE1, CHK1, SRC and RAF. Most recently I have been focused on drug design strategies that impart improved selectivity to cancer treatment, including the discovery and development of novel hypoxia-activated prodrugs. I am a co-inventor of the clinical stage prodrug tarloxotinib bromide, a first-in-class hypoxia-activated irreversible EGFR/HER2 inhibitor under license to Rain Therapeutics. I am also a co-inventor of CP-506, a hypoxia-activated prodrug recently selected for clinical trial in Europe by Convert Pharmaceuticals. I have published 42 peer-reviewed papers and 2 book chapters, while being listed as an inventor on 13 international PCT applications and 10 granted patents.

Research interests

Selected publications and creative works (Research Outputs)

  • Sansom, G. N., Kirk, N. S., Guise, C. P., Anderson, R. F., Smaill, J. B., Patterson, A. V., & Kelso, M. J. (2019). Prototyping kinase inhibitor-cytotoxin anticancer mutual prodrugs activated by tumour hypoxia: A chemical proof of concept study. Bioorganic & medicinal chemistry letters, 29 (10), 1215-1219. 10.1016/j.bmcl.2019.03.015
    Other University of Auckland co-authors: Bob Anderson, Adam Patterson
  • Lu, X., Chen, H., Patterson, A. V., Smaill, J. B., & Ding, K. (2019). Fibroblast Growth Factor Receptor 4 (FGFR4) Selective Inhibitors as Hepatocellular Carcinoma Therapy: Advances and Prospects. Journal of medicinal chemistry, 62 (6), 2905-2915. 10.1021/acs.jmedchem.8b01531
    Other University of Auckland co-authors: Adam Patterson
  • Spiegelberg, L., Houben, R., Niemans, R., de Ruysscher, D., Yaromina, A., Theys, J., ... Lambin, P. (2019). Hypoxia-activated prodrugs and (lack of) clinical progress: The need for hypoxia-based biomarker patient selection in phase III clinical trials. Clin Transl Radiat Oncol, 15, 62-69. 10.1016/j.ctro.2019.01.005
    Other University of Auckland co-authors: Adam Patterson
  • Kalyukina, M., Yosaatmadja, Y., Middleditch, M. J., Patterson, A. V., Smaill, J. B., & Squire, C. J. (2019). TAS-120 Cancer Target Binding: Defining Reactivity and Revealing the First Fibroblast Growth Factor Receptor 1 (FGFR1) Irreversible Structure. ChemMedChem, 14 (4), 494-500. 10.1002/cmdc.201800719
    Other University of Auckland co-authors: Adam Patterson, Christopher Squire, Martin Middleditch
  • Chan-Hyams, J. V. E., Copp, J. N., Smaill, J. B., Patterson, A. V., & Ackerley, D. F. (2018). Evaluating the abilities of diverse nitroaromatic prodrug metabolites to exit a model Gram negative vector for bacterial-directed enzyme-prodrug therapy. Biochemical pharmacology, 158, 192-200. 10.1016/j.bcp.2018.10.020
    Other University of Auckland co-authors: Adam Patterson
  • Lu, X., Yu, L., Zhang, Z., Ren, X., Smaill, J. B., & Ding, K. (2018). Targeting EGFRL858R/T790M and EGFRL858R/T790M/C797S resistance mutations in NSCLC: Current developments in medicinal chemistry. Medicinal research reviews, 38 (5), 1550-1581. 10.1002/med.21488
  • Niemans, R., Yaromina, A., Theys, J., Marcus, D., Ashoorzadeh, A., Abbattista, M., ... Deschoemaeker, S. (2018). EP-2327: Hypoxic cell killing by CP-506, a novel hypoxia-activated prodrug. Radiotherapy and Oncology. 10.1016/S0167-8140(18)32636-7
    URL: http://hdl.handle.net/2292/45391
    Other University of Auckland co-authors: Amir Ashoorzadeh, Adam Patterson
  • Xiang, Q., Wang, C., Zhang, Y., Xue, X., Song, M., Zhang, C., ... Hui, X. (2018). Discovery and optimization of 1-(1H-indol-1-yl)ethanone derivatives as CBP/EP300 bromodomain inhibitors for the treatment of castration-resistant prostate cancer. European journal of medicinal chemistry, 147, 238-252. 10.1016/j.ejmech.2018.01.087
    Other University of Auckland co-authors: Adam Patterson

Contact details

Primary office location

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