Associate Professor Jeff 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)

  • Rich, M. H., Sharrock, A., Ashoorzadeh, A., Patterson, A., Smaill, J. B., & Ackerley, D. F. (2020). Directed evolution of theB. subtilisnitroreductase YfkO improves activation of the PET-capable probe SN33623 and CB1954 prodrug. BIOTECHNOLOGY LETTERS10.1007/s10529-020-02992-0
    Other University of Auckland co-authors: Adam Patterson, Amir Ashoorzadeh
  • Lu, X., Smaill, J. B., & Ding, K. (2020). Allosterische Kinaseinhibitoren – Erwartungen und Chancen. Angewandte Chemie, 132 (33), 13868-13881. 10.1002/ange.201914525
  • Li, F. F., Stubbing, L. A., Kavianinia, I., Abbattista, M. R., Harris, P. W. R., Smaill, J. B., ... Brimble, M. A. (2020). Synthesis and antiproliferative activity of C- and N-terminal analogues of culicinin D. Bioorganic & medicinal chemistry letters, 30 (16)10.1016/j.bmcl.2020.127331
    Other University of Auckland co-authors: Louise Stubbing, Freda Li, Iman Kavianinia, Paul Harris, Margaret Brimble, Adam Patterson
  • Lu, X., Smaill, J. B., & Ding, K. (2020). New Promise and Opportunities for Allosteric Kinase Inhibitors. Angewandte Chemie (International ed. in English), 59 (33), 13764-13776. 10.1002/anie.201914525
  • Kavianinia, I., Stubbing, L. A., Abbattista, M. R., Harris, P. W. R., Smaill, J. B., Patterson, A. V., & Brimble, M. A. (2020). Alanine scan-guided synthesis and biological evaluation of analogues of culicinin D, a potent anticancer peptaibol. Bioorganic & medicinal chemistry letters, 30 (11)10.1016/j.bmcl.2020.127135
    Other University of Auckland co-authors: Louise Stubbing, Iman Kavianinia, Margaret Brimble, Paul Harris, Adam Patterson
  • Mowday, A. M., Lieuwes, N. G., Biemans, R., Gehlen, R., Guise, C. P., Ashoorzadeh, A., ... Lambin, P. (2020). Bugs as Trojan Horses to Target Necrotic Tumors. Paper presented at 23rd Annual Meeting of the American-Society-for-Gene-and-Cell-Therapy, ELECTR NETWORK. 12 May - 15 May 2020. MOLECULAR THERAPY. (pp. 2).
    Other University of Auckland co-authors: Amir Ashoorzadeh
  • Mowday, A. M., Copp, J. N., Syddall, S. P., Dubois, L. J., Wang, J., Lieuwes, N. G., ... Williams, E. M. (2020). E. coli nitroreductase NfsA is a reporter gene for non-invasive PET imaging in cancer gene therapy applications. Theranostics, 10 (23), 10548-10562. 10.7150/thno.46826
    Other University of Auckland co-authors: Adam Patterson, Amir Ashoorzadeh
  • Mowday, A. M., Lieuwes, N. G., Biemans, R., Guise, C. P., Ashoorzadeh, A., Zygouropoulou, M., ... Smaill, J. B. (2019). Targeting the tumour microenvironment with anaerobic bacteria. Paper presented at ESGCT 27th Annual Congress in collaboration with SETGyc Meeting, Barcelona, SPAIN. 22 October - 25 October 2019. HUMAN GENE THERAPY. (pp. 2).
    Other University of Auckland co-authors: Amir Ashoorzadeh, 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