Dr Nathan Brown BSc(Hons) FRSC

Group Leader, In Silico Medicinal Chemistry, The Institute of Cancer Research, London
Latest News

May 2017
Nathan has been elected a Fellow of The Royal Society of Chemistry.

November 2015
Nathan's new book has been published: In Silico Medicinal Chemistry.

August 2015
Nathan has been appointed to the Scientific Advisory Board of Molomics.

November 2014
Nathan is speaking at the Resources for Computational Drug Discovery 2014 at EBI, Cambridge.

October 2014
Nathan has been appointed to the Editorial Board of Advances in Drug Discovery and Development.

July 2014
We have a chapter in a new book on Drug Metabolism Prediction.

July 2014
Our recent paper on ligand-based and structure-based virtual screening was the number one most-read J. Chem. Inf. Model. last month.

June 2014
We've just been to Strasbourg for the Summer School on Chemoinformatics. So many legends speaking!

June 2014
New review article as part of the Mol. Inf. Strasbourg Summer School on Chemoinformatics is published.

June 2014
We welcome Dr Michael Carter from the Essex group in Southampton to our group as a Postdoctoral Fellow.

June 2014
Team in silico is on manoeuvres at ICCS 2014 in Noordwijkerhout. Come and say hello!

May 2014
New paper from the group on using ligand similarity in improving significance of docking results.

April 2014
Recent paper from the group selected as an F1000Prime.

March 2014
Nath delivers invited lecture at the University of York.

March 2014
Congratulations to Fabio on his move to Genentech!

January 2014
New paper by Yi published in Journal of Chemical Information and Modeling on fragment space analysis.

In Silico Medicinal Chemistry  
Bioisosteres in Medicinal Chemistry 
Scaffold Hopping in Medicinal Chemistry

nathan.brown [at] icr.ac.uk

Group Leader, In Silico Medicinal Chemistry

Cancer Research UK Cancer Therapeutics Unit

Division of Cancer Therapeutics

The Institute of Cancer Research, London, U.K.


I lead the In Silico Medicinal Chemistry group in the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research in London, supporting ChemoinformaticsMolecular ModellingChemometrics, and Computational Chemistry within the Medicinal Chemistry department.  My primary interests are in the development and application of software tools to push forward the progress of drug discovery with a particular focus on simultaneously optimising multiple objectives.  At the ICR, our group supports the activities of over 50 PhD medicinal chemists spread over a number of teams and therapeutic areas working towards novel oncology therapeutics.

I have also recently conducted research at the Universities of Sheffield, UK and Erlangen-Nuremberg, Germany, and Eli Lilly & Co. in Ascot, UK, Avantium Technologies in Amsterdam, Netherlands, and most recently the Novartis Institutes for BioMedical Research in Basel, Switzerland.

I have a wide range of experience as a software designer and developer in many different programming languages.  Using these skills I have developed a variety of novel algorithms and tools to maximise the impact of our experimental data. I have a particular interest in data visualisation using novel statistical and charting methods to disseminate information as appropriately as possible for the intended audience.

My primary interests are: virtual ligand dockingde novo molecular design, multi-objective optimisationmolecular descriptorspredictive modellinggraph theorymachine learningevolutionary algorithmsmolecular similarity and diversity, bioisosteric replacement, and scaffold hopping.

I currently review for Journal of Chemical Information and ModelingJournal of Computer-Aided Molecular DesignJournal of Molecular Graphics and ModellingJournal of CheminformaticsQSAR and Combinatorial ScienceJournal of Medicinal ChemistryNature ChemistryNature ProtocolsDrug Discovery TodayFuture Medicinal ChemistryMedicinal Chemistry CommunicationsPLoS OneBioorganic & Medicinal ChemistryRegulatory Toxicology and PharmacologyDental MaterialsCombinatorial Chemistry and High-Throughput Screening, and Chemical Engineering Science.

I sit on the committees of the UK QSAR and Chemoinformatics Group, and the Chemical Information and Computer Applications Group of The RSC. I am also on the Editorial Board of Advances in Drug Discovery and Development, and Frontiers in Chemistry: Theoretical and Computational Chemistry.

Current Group Members

  • Dr Nathan Brown - Group Leader (2007-)
  • Dr Ngai Yi Mok - Senior Scientific Officer (2012-)
  • Dr Michael Carter - Postdoctoral Research Fellow (2014-)
  • Dr Teresa Kaserer - Higher Scientific Officer (2016-)
  • Mr Josh Meyers - PhD Student (with Prof. Julian Blagg) (2013-)
  • Mr Mostafa Jamshidiha - Visiting Scientist, Imperial College (2015-)

Former Group Members

  • Dr Nicholas Firth - PhD Student (with Prof. Julian Blagg) (2011-2015)
  • Daniel Veres M.D. - Visiting Scientist (with Dr Andreas Bender) (2014)
  • Dr Fabio Broccatelli - Postdoctoral Research Fellow (2012-2014)
  • Dr Sarah Langdon - PhD Student (with Prof. Julian Blagg) (2009-2013)
  • Dr Lewis Vidler - PhD Student (with Dr Swen Hoelder) (2009-2013)
  • Dr Berry Matijssen - Postdoctoral Research Fellow (2008-2012)
  • Dr Caterina Barillari - Postdoctoral Research Fellow (2008-2011)

Career History

2007 - Present

Group Leader, In Silico Medicinal ChemistryCancer Research UK Cancer Therapeutics UnitThe Institute of Cancer Research, London, UK.

2015 - Present

Member of the Scientific Advisory Board, Molomics, Barcelona, Spain.

2004 - 2007

Presidential Research FellowNovartis Institutes for BioMedical Research, Basel, Switzerland with Prof. Peter WillettProf. Karl-Heinz Altmann, and Dr Edgar Jacoby

2002 - 2004

Marie Curie Research FellowAvantium Technologies, Amsterdam, The Netherlands, and the University of Erlangen-Nuremberg with Prof. Johnny Gasteiger and Dr Ben McKay


Ph.D. in Chemoinformatics, The University of Sheffield, Sheffield, UK, and Eli Llly & Co. with Prof. Peter Willett and Dr Richard A. Lewis


B.Sc. with Honours in Computing, The Robert Gordon University, Aberdeen, UK with Dr John McCall and Dr Deryck Brown.


  1. Brown, N. In Silico Medicinal Chemistry: Computational Approaches to Support Drug Design. The Royal Society of Chemistry, London, 2015.
  2. Brown, N. (Ed.) Scaffold Hopping in Medicinal Chemistry. Wiley-VCH, 2013.
  3. Brown, N. (Ed.) Bioisosteres in Medicinal Chemistry. Wiley-VCH, 2012.

Peer-Reviewed Articles

  1. Mok, N. Y.; Brown, N. Applications of Systematic Scaffold Enumeration to Enrich Structure-Activity Relationship Information. J. Chem. Inf. Model. 2016, in press. >>
  2. Meyers, J.; Brown, N.; Blagg, J. Mapping the 3D structure of small molecular binding sites. J. Cheminform. 2016, 8, 70. >> (Open Access)
  3. Meyers, J.; Carter, M.; Mok, N. Y.; Brown, N. On the origins of three-dimensionality in drug-like molecules. Future Med. Chem. 2016, 8(14), 1753-1767. >> (Open Access)
  4. Osborne, J. D.; Matthews, T. P.; McHardy, T.; Proisy, N.; Cheung, K.-M. J.; Lainchbury, M.; Brown, N.; Walton, M. I.; Eve, P. D.; Boxall, K. J.; Hayes, A.; Henley, A. T.; Valenti, M. R.; De Haven Brandon, A. K.; Box, G.; Jamin, Y.; Robinson, S. P.; Westwood, I. M.; van Montfort, R. L. M.; Leonard, P. M.; Lamers, M. B. A. C.; Reader, J. C.; Aherne, G. W.; Raynaud, F. I.; Eccles, S. A.; Garrett, M. D.; Collins, I. Multi-parameter lead optimization to give an oral checkpoint kinase 1 (CHK1) inhibitor clinical candidate: (R)-5-((4-((morpholin-2-ylmethyl)amino)-5- (trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737). J. Med. Chem. 2016, 59(11), 5221-5237. >> (Open Access)
  5. Welford, A. J.; Caldwell, J. J.; Liu, M.; Richards, M.; Brown, N.; Lomas, C.; Tizzard, G. J.; Pitak, M. B.; Coles, S. J.; Eccles, S. A.; Raynaud, F. I.; Collins, I. Synthesis and Evaluation of a 2,11-Cembranoid-Inspired Library. Chem. Eur. J. 2016, 22, 5657-5664. >> (Open Access)
  6. Brown, N. Chemoinformatics in the United Kingdom. Mol. Inf. Special Issue: United Kingdom, 2015. >> (Open Access)
  7. Firth, N. C.; Atrash, B.; Brown, N.; Blagg, J. MOARF, an Integrated Workflow for Multiobjective Optimization: Implementation, Synthesis, and Biological Evaluation. J. Chem. Inf. Model. 2015, 55, 1169-1180. >> (Open Access)
  8. Brown, N. Bioisosteres and Scaffold Hopping in Medicinal Chemistry. Mol. Inf. 2014, 33(6-7), 458-462. >>
  9. Broccatelli, F.; Brown, N. Best of Both Worlds: On the Complementarity of Ligand-Based and Structure-Based Virtual Screening. J. Chem. Inf. Model. 2014, 54(6), -1634-1641. >> (Open Access)
  10. Mok, N. Y.; Brenk, R.; Brown, N. Increasing the Coverage of Medicinal Chemistry-Relevant Space in Commercial Fragments Screening. J. Chem. Inf. Model. 201454(1), 79-85. >> (Open Access)
  11. Bavetsias, V.; Faisal, A.; Crumpler, S.; Brown, N.; Kosmopoulou, M.; Joshi, A.; Atrash, B.; Pérez-Fuertes, Y.; Schmitt, J. A.; Boxall, K. J.; Burke, R.; Sun, C.; Avery, S.; Bush, K.; Henley, A.; Raynaud, F. I.; Workman, P.; Bayliss, R.; Linardopoulos, S.; Blagg, J. Aurora Isoform Selectivity: Design and Synthesis of Imidazo[4,5-b]pyridine Derivatives as Highly Selective Inhibitors of Aurora-A Kinase in Cells. J. Med. Chem. 201356(22), 9122-9135. >> (Open Access)
  12. Vidler, L. R.; Filippakopoulos, P.; Fedorov, O.; Picaud, S.; Martin, S.; Tomsett, M.; Woodward, H.; Brown, N.; Knapp, S.; Hoelder, S. Discovery of Novel Small-Molecule Inhibitors of BRD4 Using Structure-Based Virtual Screening. J. Med. Chem., 2013, 56(20)8073-8088. >> (Open Access)
  13. Morley, A. D.; Pugliese, A.; Birchall, K.; Bower, J.; Brennan, P.; Brown, N.; Chapman, T.; Drysdale, M.; Gilbert, I. H.; Hoelder, S.; Jordan, A.; Ley, S. V.; Merritt, A.; Miller, D.; Swarbrick, M. E.; Wyatt, P. G. Fragment-based hit identification: thinking in 3D. Drug Discovery Today 201318(23-24), 1221-1227. >> (Open Access)
  14. Silva-Santisteban, M. C.; Westwood, I. M. ; Boxall, K.; Brown, N.; Peacock, S.; McAndrew, C.; Barrie, E.; Richards, M.; Mirza, A.; Oliver, A. W.; Burke, R.; Hoelder, S.; Jones, K.; Aherne, G. W.; Blagg, J.; Collins, I.; Garrett, M. D.; van Montfort, R. L. M. Fragment-Based Screening Maps Inhibitor Interactions in the ATP-Binding Site of Checkpoint Kinase 2. PLoS ONE 20138(6). >> (Open Access)
  15. Papadatos, G.; Brown, N. In Silico Applications of Bioisosterism in Contemporary Medicinal Chemistry Practice. Wiley Interdisciplinary Reviews: Computational Molecular Science 20133(4), 339-354>>
  16. Nicolaou, C. A.; Brown, N. Multi-objective optimization methods in drug design. Drug Discovery Today: Technol., 201310(3), e427-e435. >>
  17. Langdon, S. R.; Westwood, I. M.; van Montfort, R. L. M.; Brown, N.; Blagg, J. Scaffold-Focused Virtual Screening: Prospective Application the Discovery of TTK Inhibitors. J. Chem. Inf. Model. 201353(5), 1100-1112>> (Open Access)
  18. Bavetsias, V.; Crumpler, S.; Sun, C.; Avery, S.; Atrash, B.; Faisal, A.; Moore, A. S.; Kosmopolou, M.; Brown, N.; Sheldrake, P. W.; Bush, K.; Henley, A.; Box, G.; Valenti, M.; de Haven Brandon, A.; Raynaud, F. I.; Workman, P.; Eccles, S. A.; Bayliss, R.; Linardopoulos, Sp.; Blagg, J. Optimization of Imidazo[4,5-b]pyridine-Based Kinase Inhibitors: Identification of a Dual FLT3/Aurora Kinase Inhibitor as an Orally Bioavailable Preclinical Development Candidate for the Treatment of Acute Myeloid Leukemia. J. Med. Chem. 201255(20), 8721-8734. >> (Open Access)
  19. Firth, N. C.; Brown, N.; Blagg, J. Plane of Best Fit: A Novel Method to Characterize the Three-Dimensionality of Molecules. J. Chem. Inf. Model. 201252(10), 2516-2525. >> (Open Access)
  20. Vidler, L. R.; Brown, N.; Knapp, S.; Hoelder, S. Druggability analysis and structural classification of bromodomain acetyl-lysine binding sites. J. Med. Chem.201255(17), 7346-7359. >> (Open Access)
  21. Langdon, S. R.; Brown, N.; Blagg, J. Scaffold Diversity of Exemplified Medicinal Chemistry Space. J. Chem. Inf. Model. 201151(9), 2174-2185. >> (Open Access)
  22. Brown, N. Algorithms for Chemoinformatics. Wiley Interdisciplinary Reviews: Computational Molecular Science 20111(5), 716-726. >>
  23. Kote-Jarai, Z.; Amin Al Olama, A.; Leongamornlert, D.; Tymrakiewicz, m.; Saunders, E.; Guy, M.; Giles, G. G.; Severi, G.; Southey, M.; Hopper, J. L.; Sit, K. C.; Harris, J. M.; Batra, J.; Spurdle, A. B.; Clements, J. A.; Hamdy, F.; Neal, D.; Donovan, J.; Muir, K.; Pharoah, P. D. P.; Chanock, S. J.; Brown, N.; Benlloch, S.; Castro, E.; Mahmud, N.; O’Brien, L.; Hall, A.; Sawyer, E.; Wilkinson, R.; Easton, D. F.; Eeles, R. A. Identification of a novel prostate cancer susceptibility variant in the KLK3 gene transcript. Hum. Genet. 2011129(6), 687-694. >> (Open Access)
  24. Lubbe, S. J.; Pittman, A. M.; Matijssen, C.; Twiss, P.; Olver, B.; Lloyd, A.; Qureshi, M.; Brown, N.; Nye, E.; Stamp, G.; Blagg, J.; Houlston, R. S. Evaluation of Germline BMP4 Mutation as a Cause of Colorectal Cancer. Human Mutation 201132, E1928-E1938. >> (Open Access)
  25. Oberoi, J.; Richards, M. W.; Crumpler, S.; Brown, N.; Blagg, J.; Bayliss, R. Structural basis of poly(ADP-ribose) recognition by the multi-zinc binding domain of Checkpoint with Forkhead-associated and RING domains (CHFR). J. Biol. Chem. 2010285, 39348-39358.
  26. Bouloc, N.; Large, J. M.; Kosmopoulou, M.; Sun, C.; Faisal, A.; Matteucci, M.; Reynisson, J.; Brown, N.; Atrash, B.; Blagg, J.; McDonald, E.; Linardopoulos, S.; Bayliss, R.; Bavetsias, V. Structure-based design of imidazo[1,2-a]pyrazine derivatives as selective inhibitors of Aurora-A kinase in cells. Bioorg. Med. Chem. Lett. 201020(20), 5988-5993. >>
  27. Langdon, S. R.; Ertl, P.; Brown, N. Bioisosteric Replacement and Scaffold Hopping in Lead Generation and Optimization. Mol. Inf. 201029(5), 366-385. >>
  28. Jacoby, E.; Boettcher, A.; Mayr, L. M.; Brown, N.; Jenkins, J. L.; Kallen, J.; Engeloch, C.; Schopfer, U.; Furet, P.; Masuya, K.; Lisztwan, J. Knowledge-Based Virtual Screening: Application to the MDM4/p53 Protein-Protein Interaction. In: Jacoby, E. (ed.), Chemogenomics, Methods in Molecular Biology, vol. 575. Humana Press, 2009.
  29. Brown, N.  Chemoinformatics - an introduction for computer scientists.  ACM Comput. Surv. 200941, 1-38. >>
  30. Nicolaou, C. A.; Brown, N.; Pattichis, C. K.  Molecular Optimization Using Multi-Objective Methods.  Curr. Opin. Drug. Discov. Devel. 200710(3), 316-324.
  31. Schuffenhauer, A.; Brown, N.; Ertl, P.; Jenkins, J.; Selzer, P.; Hamon, J.; Meyer, T.  Clustering and rule-based partitions of chemical structures evaluated in the biological activity space.  J. Chem. Inf. Model. 200747(2), 325-336.
  32. Schuffenhauer, A.; Brown, N.  Chemical diversity and biological activity.  Drug Discovery Today: Technol. 20063(4), 387-395.
  33. Brown, N.; Jacoby, E.  On scaffolds and hopping in medicinal chemistry.  Mini-Rev. Med. Chem. 20066(11), 1217-1229.
  34. Brown, N.; McKay, B.; Gasteiger, J.  A novel workflow for the inverse QSPR problem using multiobjective optimization.  J. Comput.-Aided Mol. Des. 200620(5), 333-341.
  35. Ganguly, M.; Brown, N.; Schuffenhauer, A.; Ertl, P.; Gillet, V. J.; Greenidge, P. A.  Introducing the consensus weighting concept in genetic algorithms: application to interpretable discriminant analysis.  J. Chem. Inf. Model. 200646(5), 2110-2124.
  36. Brown, N.; Lewis, R. A.  Exploiting QSAR methods in lead optimization.  Curr. Opin. Drug. Discov. Devel. 20069(4), 419-424.
  37. Schuffenhauer, A.; Brown, N.; Selzer, P.; Ertl, P.; Jacoby, E.  Relationships between molecular complexity, biological activity and structural diversity.  J. Chem. Inf. Model. 200646(2), 525-535.
  38. Brown, N.; Zehender, H.; Azzaoui, K.; Schuffenhauer, A.; Mayr, L. M.; Jacoby, E.  A chemoinformatics analysis of hitlists obtained from historical SpeedScreen assays.  J. Biomol. Screen. 200611(2), 131-137.
  39. Brown, N.; McKay, B.; Gasteiger, J.  Fingal: a novel algorithm for the generation of geometric fingerprints. QSAR Comb. Sci. 200524(4), 480-484.
  40. Brown, N.; McKay, B.; Gasteiger, J.  Fingal: a novel algorithm for the generation of geometric fingerprints.  Proceedings of the 15th European Symposium on QSAR & Molecular Modelling, Istanbul, September 5th-10th2004, pp. 72-74.
  41. Brown, N.; McKay, B.; Gasteiger, J.  The de novo design of median molecules within a property range of interest.  J. Comput.-Aided Mol. Des. 200418(12), 761-771.
  42. Brown, N.; Gilardoni, F.; McKay, B.; Gasteiger, J.  A graph-based genetic algorithm and its application to the multiobjective evolution of median molecules.  J. Chem. Inf. Comput. Sci. 200444(3), 1079-1087.
  43. Brown, N.; Lewis, R. A.; Willett, P.; Wilton, D. J.  Generation and display of activity-weighted chemical hyperstructures. J. Chem. Inf. Comput. Sci. 200343(1), 288-297.
  • Brown, N.; McKay, B. Molecular entity design method. European Patent EP15894632005 Oct. 26.
  • Brown, N.; McKay, B. Molecular entity design method. U.S. Patent US20052403552005 Oct. 27.

Dr Nathan Brown BSc(Hons) FRSC ~  Group Leader, In Silico Medicinal Chemistry ~ Updated 31st May 2017