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Prof Stephen Neidle
  • 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 1986. His work has been recognised by a number of awards, including the Sosnovsky and Aventis Prizes for work on the medicinal chemistry of cancer, the Interdisciplinary and Medicinal Chemistry Awards of the Royal Society of Chemistry and the Paul Ehrlich, Kelland and Guggenheim Lectureships. 

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," "Scientific Reports" and "Methods". He chairs the editorial board of "Annual Reports in Medicinal Chemistry" (2016-) and was Chairman of the Editorial Boards of Tetrahedron Journals 2011-13 and the RSC Biomolecular Sciences book series.  Stephen Neidle was Chair of the Chemistry in Cancer Research Working Group, American Association for Cancer Research, 2011-12. He is currently a member of The Royal Society Newton Advanced Fellowships Panel and  of the “Drinkaware UK” Medical Advisory Panel.

Research Summary

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 82 in Web of Science (92 in Google Scholar).

An example of his work being translated into new therapeutic agents is given by a novel antibiotic (ridinilazole: SMT19969) directly derived from and closely related to, earlier compounds invented by him, in collaboration with Professor John Mann (formerly at Queen’s University Belfast).

Summit plc, an Oxford, UK based drug discovery company, commenced a Phase I clinical trial for ridinilazole in 2012. This orally-available small-molecule antibiotic is selective for the treatment of C. difficile infection,   a serious hospital-associated bacterial disease especially affecting the elderly. It is notoriously hard to treat with existing drugs. In 2011 it was responsible for over 2,000 deaths in the UK, and is estimated to cause nearly 30,000 deaths per annum in the USA.  It was announced in April 2013 that the Phase I trial of ridinilazole had been concluded, with very successful results. A subsequent successful proof of concept  Phase II clinical trial has shown significant superiority over the current agent of choice and Summit Therapeutics is currently planning large-scale Phase III trials. Ridinilazole has been granted Fast Track designation by the US Food and Drug Administration.

Ridinilazole itself has been developed by Summit and its biological properties have been characterized in a collaboration with the Neidle laboratory, funded by the Wellcome Trust Seeding Drug Discovery fund. Ridinilazole shows exceptional selectivity and potency for the C. difficile 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 studies are applying this approach to therapeutic areas of high unmet clinical need, in particular targeting pancreatic cancers. Lead compounds have been identified which show high activity in in vivo models for pancreatic cancer, and are currently being evaluated for further pre-clinical and clinical development, with support from the UCL Technology Fund. 

Teaching Summary

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