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)

  • 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
  • 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
  • Cavazos, A., Ma, H., Han, L., Cai, T., Zhang, Q., Harutyunyan, K., ... Andreeff, M. (2017). Pre-Clinical Activity of SN37169, a Novel Hypoxia-Activated FLT3 Inhibitor Prodrug in FLT3-Mutated AML. Paper presented at 59th Annual Meeting of the American-Society-of-Hematology (ASH), Atlanta, GA. 9 December - 12 December 2017. BLOOD. (pp. 3).
  • 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
  • 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
  • Guise, C., Abbattista, M., Mowday, A., Ashoorzadeh, A., Bull, M., Silva, S., ... Theys, J. (2017). SN36506: A rationally designed second generation analogue of PR-104 selected for clinical evaluation. Paper presented at 15th International Tumour Microenvironment Workshop, Miami, FL, USA. 27 April - 29 April 2017.
    Other University of Auckland co-authors: Maria Abbattista, Christopher Guise, Amir Ashoorzadeh, Bob Anderson, Jack Flanagan, Kevin Hicks, Adam Patterson, Matthew Bull
  • 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

Contact details

Primary office location

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