Dr. John Hadfield
School of Science, Engineering and Environment
Senior Lecturer in Medicinal Chemistry
My first degree was in Chemistry from the University of Nottingham. Following this, I studied for a PhD in Organic Chemistry at Trent Polytechnic. I worked as a Postdoctoral Scientist at the University of Warwick where I investigated the biogenesis of riboflavin.
I was then appointed to a postdoctoral position at the Paterson Institute, Christie Hospital, Manchester where I worked on developing anticancer agents. I was appointed as a Lecturer in Chemistry at the University of Salford in 2001, and Senior Lecturer in 2008
Areas of research
Commercial Development of Bioreductive Alkylating Agents, Two-Photon Activation of Stilbenes, Development of Antivascular Agents, Synthesis of Novel Chalcones to Combat Childhood Cancers, Green Synthetic Methodologies
I teach various topics at Salford: Organic Chemistry L4-6, Pharmaceutical Science, Natural Products Chemistry, Environmental Chemistry, Anticancer drugs, Biosynthesis and Carbohydrate Chemistry.
At the Paterson Institute, I gave seminars and lectures on anticancer drug design. I am Programme Leader for the MScs in Drug Design & Discovery and Biotechnology.
The over-proliferation of vasculature contributes to the onset and continuation of several diseases which include cancer, psoriasis, endometriosis and ocular disorders (diabetic retinopathy, macular degeneration). My research aims to develop several types of low molecular weight agents which have shown promise as vascular targeting agents. The primary target for these agents is the dimeric protein tubulin and the interaction of these agents with tubulin leads to the rapid destruction of over-proliferating vasculature.
The destruction of over-proliferating vasculature in the eye will have implications for the treatment of macular degeneration and diabetic retinopathy. As over-proliferation of vasculature is also responsible for endometriosis this condition should also be treatable with antivascular agents. Also the neovasculature which supplies blood and nutrients to solid tumours is targeted by antivascular agents. For both ocular diseases, endometriosis and cancer, targeting the vasculature has several potential benefits over conventional treatments:
Antivascular agents act primarily on rapidly proliferating vasculature and act on the vascular endothelial cells causing the cells to round up and block the blood vessel. The agents also tend to have a short pharmacokinetic half-life and the endothelial cells are exposed to the highest concentration of drug in circulation. Rapid clearance of the drug reduces the potential of the drug to penetrate other tissues and this leads to reduced side effects.
The cells that make up the blood vessels are not themselves malignant and are therefore unlikely to undergo genetic changes that give rise to resistance to direct acting anti-tumour agents. Vascular targeting therapy should be applicable to all solid tumours and vascular targeting agents can destroy tumours which conventional drugs can penetrate only poorly.
We have developed several agents based on the combretastatin, chalcone and benzooxepine pharmacophore. Some of the agents have shown antivascular effects with potencies as good as or better than combretastatin A-4. We have also developed a novel stereoselective two-step synthesis of combretastatin A-4. These findings have been patented. My group has also discovered a novel oxepine pharmacophore which shows potent antivascular properties.
This finding is presently being evaluated and has been patent protected. Complementary to the research into antivascular agents we are researching the potential of two-photon activation of combretastatins. This activation will isomerise non-toxic trans combretastatins to their biologically active cis isomers using visible light.
A range of kinase inhibitors are also being developed: the ability to modulate the activity of selected kinases may form the basis of a novel strategy for cancer chemo-prevention. These findings have been patented. With Onco-NX/Incanthera we have developed a quinone pro-pro drug which requires two different types of enzyme to create the biologically active species. Phase 1 Clinical Trials are planned for this agent in 2018.
- BSc, Chemistry, University of Nottingham.
- PhD, Organic Chemistry, Trent Polytechnic, Nottingham.
- Member of the Royal Society of Chemistry, Chartered Chemist.
- Chairman of Onco-NX (2011-14); presently Scientific Advisor to Incanthera.
- Editorial Board of International Journal of Medical Engineering and Informatics.