Stephen Neidle

Stephen Neidle is a British X-ray crystallographer, chemist and drug designer working at the UCL School of Pharmacy. His area of scientific research has been in nucleic acid structure and recognition, and the research topic of quadruplexes.

Early life, education and career

Stephen Neidle was born in London and educated at Hendon County Grammar School. He received a bachelor's degree in chemistry, a Ph.D. in X-ray crystallography supervised by Donald Rogers (during which he solved the structure of streptomycin).[1] and a D.Sc. in 1995, all from Imperial College London.[2] He received an ICI Fellowship for X-ray crystallographic studies with Michael B. Hursthouse at Queen Mary University of London working on natural products and pyrrole-based compounds. Subsequently he moved to the Biophysics Department, King's College London to work on the single crystal X-ray structures of nucleic acid and nucleic acid-drug complexes and was awarded a CRC (now CRUK) Career Development Award while being a Senior Research Fellow at King's College London.[2]

He moved to the Institute of Cancer Research, Sutton as a CRC (now CRUK) Life Fellow to head the Biomolecular Structure Unit, working on anticancer drug development, on the study of their complexes with nucleic acid and protein targets of clinical importance. This work lead to a high-resolution structure of a DNA quadruplex[3] and structural studies on protein-drug complexes, such as that of diaphorase with CB1954 (ChesterBeatty 1954), an anticancer prodrug. Neidle was appointed to the Chair of Biophysics at ICR in 1990, and then made Academic Dean 1997–2002.[4] He later moved to Institute of Cancer Research, Fulham Road[5] and subsequently to the first Chair of Chemical Biology at UCL School of Pharmacy. He is now Emeritus Professor of Chemical Biology at the University College London and CRUK Professorial Fellow.[2]

Research

Neidle has worked in the area of academic drug discovery and has been heavily involved in the development of drugs which recognise DNA. One of the anticancer drugs which he has been involved in developing has been abiraterone, which is used in the treatment of advanced prostate cancer.[6] More recently he and his collaborators played a key role[7] in the design of a novel antibiotic, ridinilazole, which has recently been assessed in phase III clinical trials for the treatment of Clostridium difficile infections.[8]

His current research interests centre on the development of novel therapeutic agents using fundamental aspects of the chemistry and biology of nucleic acid structure and its recognition by small molecules, using this to computationally design improved drugs with enhanced specificity. He has led in the study of G-quadruplex nucleic acids as therapeutic targets,[9][10][11][12][13] especially focussing on their structure and recognition, using structural, chemical and biological approach in an integrated multidisciplinary approach. Most recently his research group has designed several compounds showing high activity in vitro and in vivo against human cancers, in particular pancreatic cancer.[14][15] UCL Business have been instrumental in licensing these new experimental drugs in January 2022. These are being developed by Qualigen Therapeutics Inc in San Diego.[16] In January 2023 the USA Food and Drug Administration approved the lead compound QN-302 for Orphan Drug designation in pancreatic cancer. In July 2023 Qualigen Therapeutics Inc received IND clearance from the FDA to initiate a Phase 1 clinical trial of QN-302 for the treatment of advanced or metastatic solid tumors.

Neidle has published over 500 papers and reviews,[2] 14 patents, edited nine books and has written four books on nucleic acid structure, drug-DNA interactions and cancer drug discovery. His current h-index is 114 (Google Scholar).[17] He was European editor of Bioorganic & Medicinal Chemistry Letters and became its editor-in-chief 2019-2021.[18]

Honours and awards

Neidle has received various national and international awards for his work, including:[19]

  • 2022 Bioorganic and Medicinal Chemistry Letters published a Stephen Neidle Honour issue[20]
  • 2011 Distinguished Lecturer, Baptist University of Hong Kong
  • 2011 The Kelland Lecturer
  • 2008 Royal Society of Chemistry Sosnovsky Award for cancer therapy.[21]
  • 2006 Visiting Professor, La Sapienza University of Rome
  • 2005 The Guggenheim Lecturer, University of Reading
  • 2004 Prix Paul Ehrlich, Societé de Chimie Thérapeutique, France
  • 2002 Royal Society of Chemistry Interdisciplinary Award.[22]
  • 2000 Biological and Medicinal Sector Prize, Royal Society of Chemistry

References
  1. Neidle, S.; Rogers, D.; Hursthouse, M. B. (1978). "The crystal and molecular structure of streptomycin oxime selenate tetrahydrate". Proceedings of the Royal Society of London. A. Mathematical and Physical Sciences. 359 (1698): 365–388. Bibcode:1978RSPSA.359..365N. doi:10.1098/rspa.1978.0047. S2CID 96093485.
  2. "Iris View Profile". iris.ucl.ac.uk. Retrieved 2023-02-14.
  3. Parkinson, Gary N.; Lee, Michael P. H.; Neidle, Stephen (2002). "Crystal structure of parallel quadruplexes from human telomeric DNA". Nature. 417 (6891): 876–880. Bibcode:2002Natur.417..876P. doi:10.1038/nature755. PMID 12050675. S2CID 4422211.
  4. "Prof Stephen Neidle: Emeritus Professor of Chemical Biology and CRUK Professorial Fellow". ucl.ac.uk. 25 April 2018. Retrieved 2023-02-15.
  5. "Major Advance Which Will Affect Future Of Cancer Drug Development". www.icr.ac.uk. Retrieved 2023-02-14.
  6. "A new way to treat prostate cancer: The story of abiraterone". The Institute of Cancer Research. 2012-09-10. Archived from the original on 9 July 2012. Retrieved 2023-02-15.
  7. Mann J, Taylor PW, Dorgan CR, Johnson PD, Wilson FX, Vickers R, Dale AJ, Neidle S (2015). "Researchers develop entirely new antibiotic to treat gut infection". MedChemComm. 6 (8): 1420–26. doi:10.1039/c5md00238a. PMC 4756575. PMID 26949507.
  8. UCL (2022-04-12). "Researchers develop entirely new antibiotic to treat gut infections". Research Impact. Retrieved 2023-02-14.
  9. Sun, Daekyu; Thompson, Brian; Cathers, Brian E.; Salazar, Miguel; Kerwin, Sean M.; Trent, John O.; Jenkins, Terence C.; Neidle, Stephen; Hurley, Laurence H. (1997). "Inhibition of Human Telomerase by a G-Quadruplex-Interactive Compound". Journal of Medicinal Chemistry. 40 (14): 2113–2116. doi:10.1021/jm970199z. PMID 9216827.
  10. Read, Martin; Harrison, R. John; Romagnoli, Barbara; Tanious, Farial A.; Gowan, Sharon H.; Reszka, Anthony P.; Wilson, W. David; Kelland, Lloyd R.; Neidle, Stephen (2001). "Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors". Proceedings of the National Academy of Sciences. 98 (9): 4844–4849. Bibcode:2001PNAS...98.4844R. doi:10.1073/pnas.081560598. PMC 33125. PMID 11309493.
  11. Balasubramanian, Shankar; Hurley, Laurence H.; Neidle, Stephen (2011). "Targeting G-quadruplexes in gene promoters: A novel anticancer strategy?". Nature Reviews Drug Discovery. 10 (4): 261–275. doi:10.1038/nrd3428. PMC 3119469. PMID 21455236.
  12. Neidle, Stephen (2016). "Quadruplex Nucleic Acids as Novel Therapeutic Targets". Journal of Medicinal Chemistry. 59 (13): 5987–6011. doi:10.1021/acs.jmedchem.5b01835. PMID 26840940.
  13. Neidle, Stephen (2017). "Quadruplex nucleic acids as targets for anticancer therapeutics". Nature Reviews Chemistry. 1 (5). doi:10.1038/s41570-017-0041.
  14. Marchetti, Chiara; Zyner, Katherine G.; Ohnmacht, Stephan A.; Robson, Mathew; Haider, Shozeb M.; Morton, Jennifer P.; Marsico, Giovanni; Vo, Tam; Laughlin-Toth, Sarah; Ahmed, Ahmed A.; Di Vita, Gloria; Pazitna, Ingrida; Gunaratnam, Mekala; Besser, Rachael J.; Andrade, Ana C. G.; Diocou, Seckou; Pike, Jeremy A.; Tannahill, David; Pedley, R. Barbara; Evans, T. R. Jeffry; Wilson, W. David; Balasubramanian, Shankar; Neidle, Stephen (2018). "Targeting Multiple Effector Pathways in Pancreatic Ductal Adenocarcinoma with a G-Quadruplex-Binding Small Molecule". Journal of Medicinal Chemistry. 61 (6): 2500–2517. doi:10.1021/acs.jmedchem.7b01781. PMC 5867665. PMID 29356532.
  15. Ahmed, Ahmed A.; Angell, Richard; Oxenford, Sally; Worthington, Jenny; Williams, Nicole; Barton, Naomi; Fowler, Thomas G.; o'Flynn, Daniel E.; Sunose, Mihiro; McConville, Matthew; Vo, Tam; Wilson, W. David; Karim, Saadia A.; Morton, Jennifer P.; Neidle, Stephen (2020). "Asymmetrically Substituted Quadruplex-Binding Naphthalene Diimide Showing Potent Activity in Pancreatic Cancer Models". ACS Medicinal Chemistry Letters. 11 (8): 1634–1644. doi:10.1021/acsmedchemlett.0c00317. PMC 7429975. PMID 32832034.
  16. "Qualigen Therapeutics Receives Orphan Drug Designation from the U.S. Food and Drug Administration for QN-302, a G-Quadruplex (G4)". Retrieved 2023-02-14.
  17. "Stephen Neidle". Google Scholar. Retrieved 2023-02-15.
  18. Neidle, Stephen (2019). "Bioorganic & Medicinal Chemistry Letters – Editorial Board". Archived from the original on 2019-12-12. Retrieved 2023-02-12.
  19. "Prof Stephen Neidle: Achievements". iris.ucl.ac.uk. Retrieved 2023-02-14.
  20. "Bioorganic & Medicinal Chemistry Letters | Stephen Neidle Honour Issue | ScienceDirect.com by Elsevier". www.sciencedirect.com. Retrieved 2023-02-14.
  21. "George and Christine Sosnovsky Award in Cancer Therapy Winners". rsc.org. Retrieved 2023-02-12.
  22. "Interdisciplinary Prizes: Previous Winners". rsc.org. Retrieved 2023-02-12.
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