麻豆传媒

History

Dr Ian Hardcastle received his first degree from Bristol University in 1987. He received his PhD in organic synthesis in 1990, from Manchester University, with Dr Peter Quayle. This was followed by a post-doctoral fellowship in the CRC Centre for Cancer Therapeutics at The Institute of Cancer Research with Professor Mike Jarman. Work at the ICR included: studies of the structure activity relationships for tamoxifen analogues, studies into the genotoxic mechanism of tamoxifen. The development of the novel CYP17a inhibitor abiraterone (Zytiga) licenced for the treatment of castrate resistant prostate cancer. The synthesis of novel inhibitors of the Farnesyl Transferase enzyme and the development of novel template-based combinatorial libraries for lead discovery.

In November 1999 he joined the Drug Discovery Programme in the Cancer Research Unit now the 麻豆传媒 Cancer Centre at the Northern Institute for Cancer Research (NICR), 麻豆传媒, as a Lecturer in Medicinal Chemistry and is now Reader in Medicinal Chemistry.

 

Principal Research Interests: medicinal chemistry and drug discovery, targeted anti-cancer agents.

 

The medicinal chemistry team (C Cano, BT Golding, IR Hardcastle, and M Waring) is part of the Drug Discovery Group within the NICR. Working closely with basic cancer biologists, structural biologists, pharmacologists, imaging specialists, and clinical scientists, the overall aim of the programme is to discover novel small-molecule inhibitors of cancer targets which can be developed into new treatments for cancer patients.

Targets are selected based on an understanding of the underlying cancer biology and their clinical relevance. Current projects include the discovery of small-molecule MDM2-p53 protein protein interactions, the discovery of small-molecule ERK5 inhibitors, and hit-discovery studies for other novel cancer targets.

Contemporary, medicinal chemistry methods are used in all projects. including high throughput screening to identify hit compounds (through external collaborations), and structural biology to enable rational drug-design. High-throughput synthesis, utilising solution-and solid-phase multiple-parallel approaches and microwave heating, is used to determine structure-activity relationships and rapidly optimise biological activities and pharmaceutical properties for lead compounds.

Computational chemistry and informatics are essential tools, and the group uses the Dotmatics database suite, and Optibrium's StarDrop for predicting properties.

School of Natural and Environmental Sciences

BSc/MChem Chemistry and Chemistry with Medicinal Chemistry

CHY1101 - Organic Chemistry
CHY1102 - Fundamentals of Biological and Medicinal Chemistry
CHY2101 - Organic Chemistry
CHY2103 - Medicinal Chemistry
CHY3108 - Organic Chemistry
CHY3011 - Literature Project
CHY8421/8821 - Advanced Methods in Drug Discovery
CHY8411/8412 - Research Project

MSc Drug Chemistry

CHY8821 - Modern Methods in Drug Discovery
CHY8812 - Research Preparation

CHY8827 - Biological and Medicinal Chemistry

Medical School

MRes Translational Medicine and Therapeutics - L12 The role of medicinal chemistry

• Wood D, Lopez-Fernandez JD, Knight LE, Al-Khawaldeh I, Gai C, Lin S, Martin MP, Miller DC, Cano C, Endicott JA, Hardcastle IR, Noble MEM, Waring MJ. . Journal of Medicinal Chemistry 2019, 62(7), 3741-3752.
• Hill SL, Dunn M, Cano C, Harnor SJ, Hardcastle IR, Grundlingh J, Dargan PI, Wood DM, Tucker S, Bartram T, Thomas SHL. . Clinical Chemistry 2018, 64(2), 346-354.
• Miller DC, Martin MP, Adhikari S, Brennan A, Endicott JA, Golding BT, Hardcastle IR, Heptinstall A, Hobson S, Jennings C, Molyneux L, Ng Y, Wedge SR, Noble MEM, Cano C. . Organic and Biomolecular Chemistry 2018, 16(11), 1843-1850.
• Heptinstall AB, Adiyasa IWS, Cano C, Hardcastle IR. . Future Medicinal Chemistry 2018, 10(11), 1369–1388.
• Coxon C, Anscombe E, Harnor S, Martin M, Carbain B, Golding B, Hardcastle I, Harlow L, Korolchuk S, Matheson C, Newell D, Noble M, Sivaprakasam M, Tudhope SJ, Turner D, Wang L, Wedge SR, Wong C, Griffin R, Endicott J, Cano C. . Journal of Medicinal Chemistry 2017, 60, 1746-1767.
• Chessari G, Howard S, Buck IM, Cons BD, Johnson CN, Holvey RS, Rees DC, St Denis JD, Tamanini E, Golding BT, Hardcastle IR, Cano CF, Miller DC, Noble MEM, Griffin RJ, Osborne JD, Peach J, Lewis A, Hirst KL, Whittaker BP, Watson DR. . PCT/GB2016/053041, 06/04/2017.
• Chessari G, Howard S, Buck IM, Cons BD, Johnson CN, Holvey RS, Rees DC, StDenis JD, Tamanini E, Golding BT, Hardcastle IR, Cano CF, Miller DC, Noble MEM, Osborne JD, Peach J, Lewis A, Hirst KL, Whittaker BP, Watson DW, Mitchell DR, Griffin RJ. . WO/2017055859, 06/04/2017.
• Hardcastle IR. . In: Bernstein, PR; Georg, GI; Keller, Th; Kobayashi, T; Lowe, JA; Meanwell, NA; Saxena, AK; Stilz, U; Supuran, CT; Zhang, A, ed. Topics in Medicinal Chemistry. Berlin, Heidelberg: Springer, 2017, pp.1-35.
• Hardcastle IR. . In: Chackalamannil,S;Rotella,DP;Ward,SE, ed. Comprehensive Medicinal Chemistry III. Elsevier, 2017, pp.154-201.
• Coxon RC, Wong C, Bayliss R, Boxall K, Carr KH, Fry AM, Hardcastle IR, Matheson CJ, Newell DR, Sivaprakasam M, Thomas H, Turner D, Yeoh S, Wang LZ, Griffin RJ, Golding BT, Cano C. . Oncotarget 2017, 8, 19089-19124.
• Drummond CJ, Esfandiari A, Liu J, Lu X, Hutton C, Jackson J, Bennaceur K, Xu Q, Makimanejavali AR, Bello FD, Piergentili A, Newell DR, Hardcastle IR, Griffin RJ, Lunec J. . Oncotarget 2016, 7(29), 46203-46218.
• Myers SM, Bawn RH, Bisset LC, Blackburn TJ, Cottyn B, Molyneux L, Wong AC, Cano C, Clegg W, Harrington RW, Leung H, Rigoreau L, Vidot S, Golding BT, Griffin RJ, Hammonds T, Newell DR, Hardcastle IR. . ACS Combinatorial Science 2016, 18(8), 444-455.
• Reuillon T, Miller D, Myers S, Molyneux L, Cano C, Hardcastle I, Griffin R, Rigoreau L, Golding B, Noble M. . WO/2016/042341, 24/03/2016.
• Rasheed OK, Hardcastle IR, Raftery J, Quayle P. . Organic & Biomolecular Chemistry 2015, 13(29), 8048-8052.
• Zaytsev A, Dodd B, Magnani M, Ghiron C, Golding BT, Griffin RJ, Liu J, Lu X, Micco I, Newell DR, Padova A, Robertson G, Lunec J, Hardcastle IR. . Chemical Biology and Drug Discovery 2015, 86(2), 180-189.
• Zhang B, Golding BT, Hardcastle IR. . Future Medicinal Chemistry 2015, 7(5), 631-645.
• Carbain B, Paterson DJ, Anscombe E, Campbell AJ, Cano C, Echalier A, Endicott JA, Golding BT, Haggerty K, Hardcastle IR, Jewsbury PJ, Newell DR, Noble MEM, Roche C, Wang LZ, Griffin RJ. . Journal of Medicinal Chemistry 2014, 57(1), 56-70.
• Anil B, Blackburn E, Blackburn T, Cully S, Liu J, Drummond CJ, Endicott JA, Golding BT, Griffin RJ, Haggerty K, Lunec J, Newell DR, Revill CH, Riedinger C, Watson AF, Xu Q, Zhao Y, Hardcastle IR, Noble MEM. . In: 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. 2014, Barcelona, Spain: Elsevier.
• Myers S, Martin N, Bawn R, Blackburn T, Barrett L, Reuillon T, Golding B, Griffin R, Hammonds T, Hardcastle I, Leung H, Newell D, Rigoreau L, Wong A, Cano C. . In: 26th EORTC – NCI – AACR Symposium on Molecular Targets and Cancer Therapeutics. 2014, Barcelona, Spain: Elsevier.
• Lebraud H, Coxon CR, Archard VS, Bawn CM, Carbain B, Matheson CJ, Turner DM, Cano C, Griffin RJ, Hardcastle IR, Baisch U, Harrington RW, Golding BT. . Organic & Biomolecular Chemistry 2014, 12, 141-148.
• Cinatl J, Speidel D, Hardcastle I, Michelis M. . Biochemical Society Transactions 2014, 42(4), 752–757.
• Hardcastle IR. . In: Neidle, S, ed. Cancer drug design and discovery. Elsevier, Academic Press, 2014, pp.391-426.
• Carbain B, Coxon CR, Lebraud H, Elliott KJ, Matheson CJ, Meschini E, Roberts AR, Turner DM, Wong C, Cano C, Griffin RJ, Hardcastle IR, Golding BT. . Chemistry: A European Journal 2014, 20(8), 2311-2317.
• Cano C, Saravanan K, Bailey C, Bardos J, Curtin NJ, Frigerio M, Golding BT, Hardcastle IR, Hummersone MG, Menear KA, Newell DR, Richardson CJ, Shea K, Smith GCM, Thommes P, Ting A, Griffin RJ. . Journal of Medicinal Chemistry 2013, 56(16), 6386-6401.
• Blackburn TJ, Ahmed S, Coxon CR, Liu JF, Lu XH, Golding BT, Griffin RJ, Hutton C, Newell DR, Ojo S, Watson AF, Zaytzev A, Zhao Y, Lunec J, Hardcastle IR. . MedChemComm 2013, 4(9), 1297-1304.
• Lebraud H, Cano C, Carbain B, Hardcastle IR, Harrington RW, Griffin RJ, Golding BT. . Organic & Biomolecular Chemistry 2013, 11(11), 1874-1878.
• Coffey K, Blackburn TJ, Cook S, Golding BT, Griffin RJ, Hardcastle IR, Hewitt L, Huberman K, McNeill HV, Newell DR, Roche C, Ryan-Munden CA, Watson A, Robson CN. . PLoS One 2012, 7(10), e45539.
• Clapham KM, Rennison T, Jones G, Craven F, Bardos J, Golding BT, Griffin RJ, Haggerty K, Hardcastle IR, Thommes P, Ting A, Cano C. . Organic & Biomolecular Chemistry 2012, 10(33), 6747-6757.
• Clapham KM, Bardos J, Finlay R, Golding BT, Griffen EJ, Griffin RJ, Hardcastle IR, Menear KA, Ting A, Turner P, Young GL, Cano C. . Bioorganic & Medicinal Chemistry Letters 2011, 21(3), 966-970.
• Hardcastle IR, Liu J, Valeur E, Watson A, Ahmed SU, Blackburn TJ, Bennaceur K, Clegg W, Drummond C, Endicott JA, Golding BT, Griffin RJ, Gruber J, Haggerty K, Harrington RW, Hutton C, Kemp S, Lu X, McDonnell JM, Newell DR, Noble ME, Payne SL, Revill CH, Riedinger C, Xu Q, Lunec J. . Journal of Medicinal Chemistry 2011, 54(5), 1233-1243.
• Watson AF, Liu JF, Bennaceur K, Drummond CJ, Endicott JA, Golding BT, Griffin RJ, Haggerty K, Lu XH, McDonnell JM, Newell DR, Noble MEM, Revill CH, Riedinger C, Xu Q, Zhao Y, Lunec J, Hardcastle IR. . Bioorganic & Medicinal Chemistry Letters 2011, 21(19), 5916-5919.
• Thomas HD, Wang LZ, Roche C, Bentley J, Cheng YZ, Hardcastle IR, Golding BT, Griffin RJ, Curtin NJ, Newell DR. . European Journal of Cancer 2011, 47(13), 2052-2059.
• Riedinger C, Noble ME, Wright DJ, Mulks F, Hardcastle I, Endicott JA, McDonnell JM. . Chemical Biology and Drug Design 2011, 77(5), 301-308.
• Rodriguez SA, Clapham KM, Barrett L, Cano C, Desage ME, Griffin RJ, Hardcastle IR, Payne SL, Rennison T, Richardson C, Golding BT. . Organic & Biomolecular Chemistry 2011, 9(17), 6066-6074.
• Cano C, Golding BT, Haggerty K, Hardcastle IR, Peacock M, Griffin RJ. . Organic & Biomolecular Chemistry 2010, 8(8), 1922-1928.
• Cano C, Barbeau OR, Bailey C, Cockcroft XL, Curtin NJ, Duggan H, Frigerio M, Golding BT, Hardcastle IR, Hummersone MG, Knights C, Menear KA, Newell DR, Richardson CJ, Smith GC, Spittle B, Griffin RJ. . Journal of Medicinal Chemistry 2010, 53(24), 8498-8507.
• Payne SL, Rodriguez-Aristegui S, Bardos J, Cano C, Golding BT, Hardcastle IR, Peacock M, Parveen N, Griffin RJ. . Bioorganic & Medicinal Chemistry Letters 2010, 20(12), 3649-3653.
• Marchetti F, Cano C, Curtin NJ, Golding BT, Griffin RJ, Haggerty K, Newell DR, Parsons RJ, Payne SL, Wang LZ, Hardcastle IR. . Organic & Biomolecular Chemistry 2010, 8(10), 2397-2407.
• Wong C, Griffin RJ, Hardcastle IR, Northen JS, Wang LZ, Golding BT. . Organic & Biomolecular Chemistry 2010, 8(10), 2457-2464.
• Murr M, Cano C, Golding BT, Hardcastle IR, Hummersome M, Frigerio M, Curtin NJ, Menear K, Richardson C, Smith G, Griffin R. . Bioorganic and Medicinal Chemistry Letters 2008, 18(17), 4885-4890.
• Riedinger C, Endicott JA, Kemp SJ, Smyth LA, Watson A, Valeur E, Golding BT, Griffin RJ, Hardcastle IR, Noble ME, McDonnell JM. . Journal of the American Chemical Society 2008, 130(47), 16038-16044.
• Hardcastle IR. . Drugs of the Future 2007, 32(10), 883-896.
• Hollick J, Rigoreau L, Cano-Soumillac C, Cockcroft X, Curtin NJ, Frigerio M, Golding BT, Guiard S, Hardcastle IR, Hickson I, Hummersone M, Menear K, Martin N, Matthews I, Newell DR, Ord R, Richardson C, Smith G, Griffin RJ. . Journal of Medicinal Chemistry 2007, 50(8), 1958-1972.
• Barbeau OR, Cano-Soumillac C, Griffin RJ, Hardcastle IR, Smith GCM, Richardson C, Clegg W, Harrington RW, Golding BT. . Organic & Biomolecular Chemistry 2007, 5(16), 2670-2677.
• Hardcastle, I.R., Ahmed, S., Atkins, H., Farnie, G., Golding, B.T., Griffin, R.J., Guyenne, S., Hutton,C., Källblad, P., Kemp, S., Kitching, M.S., Newell, D.R., Norbedo, S., Northen, J.S., Reid, R.J., Saravanan, K., Willems, H., Lunec, J. . Journal of Medicinal Chemistry 2006, 49(21), 6209-6221.
• Hardcastle I, Ahmed S, Atkins H, Calvert AH, Curtin NJ, Farnie G, Golding BT, Griffin R, Guyenne S, Hutton C, Källblad P, Kemp S, Kitching M, Newell D, Norbedo S, Northen J, Reid R, Saravanan K, Willems H, Lunec J. . Bioorganic and Medicinal Chemistry Letters 2005, 15(5), 1515-1520.