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- Emeritus Professor of Chemical Biology and CRUK Professorial Fellow
- UCL School of Pharmacy
- Faculty of Life Sciences
Professor Stephen Neidle is a chemistry graduate of Imperial College, where he also undertook research on the structures of a number of complex natural products and antibiotics (DSc, PhD, ARCS).. After a period as an ICI Fellow, he joined the Biophysics Department at King’s College London, which initiated his interest in nucleic acid structural studies. He was one of the first Cancer Research Campaign Career Development Awardees, and has been a Life Fellow and Professorial Fellow of Cancer Research UK since 2002.
He was appointed to the Chair of Biophysics at the Institute of Cancer Research in 1990 (where he was also Academic Dean 1997-2002) and moved to the School of Pharmacy, University of London in 2002 as the first holder of the new Chair of Chemical Biology. He has also been Research Director of the School.
Stephen Neidle is Editor-in-Chief of "Bioorganic and Medicinal Chemistry Letters", and is a member of the editorial boards of the journals "Nucleic Acids Research" and "Methods". He was Chairman of the Editorial Board of Tetrahedron Journals 2011-13, and chaired the RSC Biomolecular Sciences book series. He is currently a member of the Wellcome Trust Peer Review College and The Royal Society Newton Fellows Panel.
Stephen Neidle’s interests are primarily in the chemistry and biology of nucleic acid structure and recognition by small molecules, and in exploiting this information for the rational design of novel anti-cancer and anti-infective agents. He has pioneered studies on the structure and recognition of G-quadruplex nucleic acids as therapeutic targets, using an integrated multi-disciplinary structural, chemical and biological approach. He has published nearly 500 papers and reviews, together with 14 patents, and has written and edited a number of books on nucleic acids, drug-DNA interactions and cancer drug discovery. His current h index is 80 in Web of Science (90 in Google Scholar).
An example of his work being translated into new therapeutic agents is given by a novel antibiotic (ridinilazole: SMT19969) derived from and closely related to, earlier compounds invented by Stephen Neidle, in collaboration with Professor John Mann (formerly at Queen’s University Belfast, now a visiting professor at UCL).
Summit plc, an Oxford, UK based drug discovery company, commenced a Phase I clinical trial for ridinilazole in 2012. This novel orally-available small-molecule antibiotic is selective for the treatment of C. difficile infections. C. difficile is a serious hospital-associated bacterial disease especially affects the elderly and is hard to treat with existing drugs. In 2011 it was responsible for over 2,000 deaths in the UK, and is estimated to cause over 30,000 deaths in the USA. It was announced in April 2013 that the Phase I trial had been concluded, with very successful results. A Phase II clinical trial started in 2015 and early results are already encouraging, showing significant superiority over the current agent of choice..
Ridinilazole itself has been developed by Summit and its biological properties have been characterized in collaboration with the Neidle laboratory. The collaboration was funded by the Wellcome Trust Seeding Drug Discovery fund. Ridinilazole shows exceptional selectivity and potency for the bacterium and pre-clinical data indicated that it has remarkably low toxicity coupled with good tolerance in humans, which has been confirmed by the Phase I and II trials.
Work in the Neidle laboratory in the cancer therapeutics area is currently focussed on exploiting the occurrence of quadruplex DNA and RNA sequences in particular regions of the human genome associated with aberrant telomere maintenance, genomic instability or oncogene expression, and targeting these with selective small molecules. Recent work is applying this approach to two principal therapeutic areas, targeting pancreatic and renal cancers. Lead compounds have been identified which show high activity in in vivo models for pancreatic cancer, and are currently being evaluated for further development.