Newcastle University

Introduction

Herbie Newell is Professor of Cancer Therapeutics at the Northern Institute for Cancer Research. He has over 30 years experience of the development of conventional and novel cancer chemotherapies.

Roles and Responsibilities

Professor of Cancer Therapeutics
Northern Institute for Cancer Research

Qualifications

1979 Membership of the Institute of Biology by Examination in Pharmacology

1984 University of London - PhD Pharmacology

Previous Positions

1989-1995 Cancer Research Unit, University of Newcastle, Newcastle upon Tyne
Senior Lecturer

1988-1989 Clinical Pharmacology Team, Drug Development Section, Institute of Cancer Research, Sutton, Surrey
Grade 1 Scientist

1984-1988 Department of Biochemical Pharmacology, Institute of Cancer Research, Sutton, Surrey
Grade 2 Scientist

1976-1984 Department of Biochemical Pharmacology, Institute of Cancer Research, Sutton, Surrey
Research Officer

Memberships

Preclinical Chair of the Cancer Research UK Phase I/II Committee
Chair of the Cancer Research UK New Agents Committee
Cancer Research UK Programme Grants Committee
Cancer Research UK Translational Research Committee
Cancer Research Campaign Chemical Collection ad hoc Committee
EORTC Pharmacology and Molecular Mechanisms Group Committee
United Kingdom Children's Cancer Study Group New Agents Committee
Newcastle University Faculty of Medicine Research Committee
Newcastle Hospital Joint Research Executive Scientific Committee
RAE 2001 UoA 9 (Pharmacy) Panel Member
British Association for Cancer Research - Chair Executive Committee
American Association for Cancer Research

Languages

English

Research Interests

Cancer pharmacology
Drug development
Pharmacokinetics of anticancer drugs
DNA repair modulation
Kinase inhibitors

Other Expertise

Translational cancer research
Early clinical trials in cancer

Current Work

The development of inhibitors of:
Cyclin dependent kinases
DNA damage related kinases
Receptor tyrosine kinases
DNA repair enzymes and proteins
Pharmacologically-guided dosing in adults and children

Future Research

The development of:
Selective antitumour agents
Non-invasive imaging methodology for pharmacokinetic and pharmacodynamic studies

Research Roles

Professor of Cancer Therapeutics
Northern Institute for Cancer Research

Postgraduate Supervision

PhD Student Supervisor

Esteem Indicators

2004 Michel Clavel Award Lecturer at the 16th EORTC/NCI/AACR New Drugs Conference, Geneva

Funding

"Newcastle Paediatric Pharmacology UKCCSG - CRC Site Visit" Cancer Research Campaign. Jan 2000 - Jan 2004. £71,130 per annum. Held with AV Boddy and ADJ Pearson.

"Synthesis and evaluation of novel inhibitors of DNA-dependent protein kinase (DNA-PK)" BBSRC Industrial CASE studentship with KuDOS Pharmaceuticals. Oct 2000 - Oct 2003. £54,210. Held with AH Calvert, NJ Curtin, BT Golding and RJ Griffin.

"Combinatorial synthesis of libraries of small molecule modulators of signal transduction pathways" EPSRC quota studentship. Oct 2000 - Oct 2003. £40,000. Held with (PI) AH Calvert, NJ Curtin, BT Golding, RJ Griffin and I Hardcastle.

"Potentiation of thymidylate synthase inhibition by tumour-specific thymidine depletion" Cancer Research Campaign. Oct 2000 - Oct 2003. £44,461. Held with AV Boddy and GA Taylor.

"Design and synthesis of selective DNA-dependent protein kinase (DNA-PK) inhibitors" Cancer Research Campaign. Oct 2001 - Oct 2004. £64,000. Held with AH Calvert, NJ Curtin, BT Golding, RJ Griffin and IR Hardcastle.

"The synthesis of DNA-dependent protein kinase inhibitors" KuDOS pharmaceuticals. Equipment grant, 2001. £62,000. Held with AH Calvert, NJ Curtin, BT Golding RJ Griffin and IR Harcastle.

"Development of pharmacodynamic assays for the clinical evaluation of novel PARP inhibitors, and pre-clinical investigations of backup compounds" Agouron Pfizer GRD. Jan 2001-Jan 2002. £107,500. Held with AV Boddy, NJ Curtin, AH Calvert and BW Durkacz.

"Clerical support in recognition of contributions to CRC Committees" Cancer Research Campaign. Sept 2000 - Date. £14,818 per annum.

"Molecular Mechanisms of Disease Progression and Novel Treatments for Prostate Cancer" NCRI/MRC. Oct 2001 - Oct 2006. £1,627,389. Held with IR Hardcastle, HY Leung, DE Neal and CN Robson.

"Design, synthesis and evaluation of novel CDK inhibitors" AstraZeneca Pharmaceuticals. 2002-2004. £100,000. Held with AH Calvert, NJ Curtin, RJ Griffin, BT Golding and IR Hardcastle.:

"Preclinical and pharmacodynamic studies with novel DNA-PK inhibitors" KuDos Pharmaceuticals. Jan 2002 - Jan 2004. £183,394. Held with AH Calvert, NJ Curtin, BW Durkacz, BT Golding RJ Griffin and IR Hardcastle.

"Cancer Research UK Developmental Therapeutics Programme" Joint Director with AH Calvert. Oct 2002 - Sept 2007. £1,000,000 per annum.

"Establishment of Newcastle as a National Translational Cancer Research Network (NTRAC) Centre. Department of Health. Held with AV Boddy, AH Calvert, A Chippendale, HY Leung, D Ellison, M Verrill. June 2003 - May 2008. £1,080,000.

Industrial Relevance

Member of Scientific Advisory Panels for:
Astex Technology, AstraZenenca, Eisia Pharmaceuticals, OSI Pharmaceuticals, Viscum AG, Xenova

Patents

JONES T.R., JACKMAN A.L. and NEWELL D.R. (1986): Anticancer quinazoline derivatives. UK and Foreign Patent No. 8513754.

GRIFFIN, R. J., CALVERT, A. H., CURTIN, N. J., NEWELL, D. R., AND GOLDING, B. T. Benzamide Analogues ADPRT (PARP) Inhibitors Patent Application Number PCT/GB95/00513

GRIFFIN, R. J., CALVERT, A. H., CURTIN, N. J., NEWELL, D. R. AND GOLDING, B. T. Benzimidazole PARP Inhibitors. Patent Application Number PCT/GB96/01832.

GRIFFIN, R. J., CALVERT, A. H., CURTIN, N. J., NEWELL, D. R. AND GOLDING, B. T. Prodrugs of PARP Inhibitors. Patent Application Number 9702701.5

GRIFFIN, R. J., CALVERT, A. H., CURTIN, N. J., NEWELL, D. R. AND GOLDING, B. T. Pyrimidopyrimidine Compounds. Patent Application Number 9706618.7.

GRIFFIN, R. J., CALVERT, A. H., CURTIN, N. J., NEWELL, D. R. AND GOLDING, B. T., ENDICOTT, J.A., NOBLE, M.E.M., BOYLE, F.T. AND JEWSBURY, P.J. Purine CDK Inhibitors. Patent Application Number 9714603.9

GRIFFIN, R. J., CALVERT, A. H., CURTIN, N. J., NEWELL, D. R. AND GOLDING, B. T. ENDICOTT, J.A., NOBLE, M.E.M., BOYLE, F.T. AND JEWSBURY, P.J. Pyrimidine CDK Inhibitors. Patent Application Number 9806739.0

GRIFFIN, R. J., CALVERT, A. H., CURTIN, N. J., NEWELL, D. R. AND GOLDING, B. T. Dipyridamole analogues. Patent Application Number PCT/GB98/00966

GRIFFIN, R. J., CALVERT, A. H., CURTIN, N. J., NEWELL, D. R. AND GOLDING, B. T. Anilinopurine CDK inhibitors. Patent Application Number PCT/GB01/101686.4

GRIFFIN, R. J., CALVERT, A. H., CURTIN, N. J., NEWELL, D. R., GOLDING, B. T. HARDCASTLE, I.R., MARTIN, N., SMITH, G.C.M., RAYNAUD, F. AND WORKMAN, P. DNA-PK inhibitors - 1. Patent Application Number PCT/GB01/19865.4

GRIFFIN, R. J., CALVERT, A. H., CURTIN, N. J., NEWELL, D. R., GOLDING, B. T. HARDCASTLE, I.R., MARTIN, N., SMITH, G.C.M., RAYNAUD, F. AND WORKMAN, P. DNA-PK inhibitors - 2. Patent Application Number PCT/GB01/19863.9

WALLING, J.M., WEBB, H.K., CALVERT, A.H. AND NEWELL, D.R. Lometrexol combination therapy. Patent Application Number 10/010,740.

• Tavecchio M, Munck JM, Cano C, Newell DR, Curtin NJ. Further characterisation of the cellular activity of the DNA-PK inhibitor, NU7441, reveals potential cross-talk with homologous recombination. Cancer Chemotherapy and Pharmacology 2012, 69(1), 155-164.
• de Brito LR, Batey MA, Zhao Y, Squires MS, Maitland H, Leung HY, Hall AG, Jackson G, Newell DR, Irving JAE. Comparative pre-clinical evaluation of receptor tyrosine kinase inhibitors for the treatment of multiple myeloma. Leukemia Research 2011, 35(9), 1233-1240.
• Johnson N, Li YC, Walton ZE, Cheng KA, Li DA, Rodig SJ, Moreau LA, Unitt C, Bronson RT, Thomas HD, Newell DR, D'Andrea AD, Curtin NJ, Wong KK, Shapiro GI. Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition. Nature Medicine 2011, 17(7), 875-882.
• 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. Isoindolinone Inhibitors of the Murine Double Minute 2 (MDM2)-p53 Protein-Protein Interaction: Structure-ActivityStudies Leading to Improved Potency. 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. MDM2-p53 protein-protein interaction inhibitors: A-ring substituted isoindolinones. Bioorganic & Medicinal Chemistry Letters 2011, 21(19), 5916-5919.
• Saravanan K, Barlow HC, Barton M, Calvert AH, Golding BT, Newell DR, Northen JS, Curtin NJ, Thomas HD, Griffin RJ. Nucleoside Transport Inhibitors: Structure-Activity Relationships for Pyrimido[5,4-d]pyrimidine Derivatives That Potentiate Pemetrexed Cytotoxicity in the Presence of alpha(1)-Acid Glycoprotein. Journal of Medicinal Chemistry 2011, 54(6), 1847-1859.
• Squires M, Ward G, Saxty G, Berdini V, Cleasby A, King P, Angibaud P, Perera T, Fazal L, Ross D, Jones CG, Madin A, Benning RK, Vickerstaffe E, O'Brien A, Frederickson M, Reader M, Hamlett C, Batey MA, Rich S, Carr M, Miller D, Feltell R, Thiru A, Bethell S, Devine LA, Graham BL, Pike A, Cosme J, Lewis EJ, Freyne E, Lyons J, Irving J, Murray C, Newell DR, Thompson NT. Potent, Selective Inhibitors of Fibroblast Growth Factor Receptor Define Fibroblast Growth Factor Dependence in Preclinical Cancer Models. Molecular Cancer Therapeutics 2011, 10(9), 1542-1552.
• Thomas HD, Wang LZ, Roche C, Bentley J, Cheng YZ, Hardcastle IR, Golding BT, Griffin RJ, Curtin NJ, Newell DR. Preclinical in vitro and in vivo evaluation of the potent and specific cyclin-dependent kinase 2 inhibitor NU6102 and a water soluble prodrug NU6301. European Journal of Cancer 2011, 47(13), 2052-2059.
• Pridgeon SW, Heer R, Taylor GA, Newell DR, O'Toole K, Robinson M, Xu YZ, Karran P, Boddy AV. Thiothymidine combined with UVA as a potential novel therapy for bladder cancer. British Journal of Cancer 2011, 104(12), 1869-1876.
• Meschini E, Endicott JA, Golding BT, Hardcastle IR, Newell DR, Noble MEM, Wang LZ, Griffin RJ. Design and synthesis of dual CDK2 and CDK7 inhibitors. In: Abstracts of Papers of the American Chemical Society. 2010, American Chemical Society.
• Clapham KM, Rennison T, Rodriguez-Aristegui S, Bardos J, Curtin NJ, Golding BT, Hardcastle IR, Newell DR, Cano C, Griffin RJ. Development of potent inhibitors of DNA-dependent protein kinase (DNA-PK). In: EJC Supplements: 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. 2010, Berlin, Germany: Pergamon.
• Carbain B, Roche C, Endicott JA, Golding BT, Hardcastle IR, Cano C, Zhen-Wang L, Newell DR, Noble MEM, Griffin RJ. Structure-based design of C8-substituted O6-alkylguanine CDK1 and 2 inhibitors. In: European Journal of Cancer Supplements: 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. 2010, Berlin: Elsevier.
• Cornell L, Munck JM, Budhisetiawan F, Newell DR, Bardos JI, Manas D, Curtin NJ, Reeves H. Synthetic lethality in liver cancer cell lines treated with inhibitors of DNA double strand break repair. In: 61st Annual Meeting of the American Association for the Study of Liver Diseases. 2010, Boston, MA: Hepatology: Wiley-Blackwell.
• Watson AF, Golding BT, Griffin RJ, Hutton C, Liu JF, Lug XH, Lunec J, Newell DR, Valeur E, Hardcastle IR. MEDI 147-Isoindolinone-based inhibitors of the MDM2-p53 protein-protein interaction. In: Abstracts of Papers of the American Chemical Society: 236th National Meeting of the American Chemical Society. 2008, Philadelphia, Pennsylvania, USA: American Chemical Society.
• Calabrese C, Almassy R, Barton S, Batey M, Calvert AH, Canan-Koch S, Durkacz B, Hostomsky Z, Kumpf R, Kyle S, Li J, Maegley K, Newell DR, Notarianni E, Stratford I, Skalitzky D, Thomas HD, Wang L, Webber S, William K, Curtin NJ. Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. Journal of the National Cancer Institute 2004, 96(1), 56-67.
• Newell DR, Silvester J, McDowell C, Burtles SS. The Cancer Research UK experience of pre-clinical toxicology studies to support early clinical trials with novel cancer therapies. European Journal of Cancer 2004, 40(6), 899-906.
• Wells, P., Aboagye, E., Gunn, R., Osman, S., Boddy, A. V., Taylor, G. A., Rafi, I., Hughes, A. N., Calvert, A. H., Price, P., Newell, D. R. 2-[¹¹C]thymidine positron emission tomography as an indicator of thymidylate synthase inhibition in patients treated with AG337. Journal of the National Cancer Institute 2003, 95(9), 675-682.
• Davies T, Bentley J, Arris CE, Boyle FT, Curtin NJ, Endicott J, Gibson A, Golding BT, Griffin RJ, Hardcastle IR, Jewsbury, P., Johnson, L., Mesguiche, V., Newell, D.R., Noble, M., Tucker, J.A., Wang, L., Whitfield, H.J. Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor. Nature Structural Biology 2002, 9(10), 745-749.
• Davies TG, Endicott JA, Noble ME, Johnson LN, Arris CE, Bentley J, Boyle FT, Calvert AH, Curtin NJ, Jewsberry PJ, Gibson AE, Golding BT, Griffin RJ, Hardcastle I, Mesguiche V, Parsons R, Whitfield H, Newell DR. Structural and thermodynamic validation of inactive cdk2 as a template for structure-based drug design. Cellular and Molecular Biology Letters 2001, 6(2B), 514-515.
• Davies TG, Endicott JA, Johnson LN, Noble ME, Arris CE, Bentley J, Calvert AH, Curtin NJ, Golding BT, Griffin RJ, Hardcastle IH, Mesguiche V, Newell H, Parsons RJ, Whitfield HJ, Boyle T, Jewsbury P. Structure based design of a potent inhibitor of cdk2. Cellular and Molecular Biology Letters 2001, 6(2B), 470.
• Griffin RJ, Arris CE, Calvert AH, Curtin NJ, Jewsbury P, Endicott JA, Gibson AE, Boyle FT, Golding BT, Grant S, Johnson LN, Noble MEM, Newell DR, Lawrie A. Design, synthesis, and biological evaluation of O-6-alkylguanine and O-4-alkylpyrimidine cyclin-dependent kinase inhibitors. Abstracts of Papers of the American Chemical Society 2000, 219(2), U55 296-MEDI.
• Arris CE, Boyle FT, Calvert AH, Curtin NJ, Endicott JA, Garman EF, Gibson AE, Golding BT, Grant S, Griffin RJ, Jewsbury P, Johnson LN, Lawrie AM, Newell DR, Noble MEM, Sausville EA, Schultz R, Yu W. Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. Journal of Medicinal Chemistry 2000, 43(15), 2797-2804.
• Bentley J, Arris CE, Boyle FT, Calvert AH, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Grant S, Griffin RJ, Jewsbury PJ, Johnson LN, Noble MEM, Newell DR. Structure-activity relationships and cellular effects of novel purine- and pyrimidine-based cyclin dependent kinase inhibitors. Clinical Cancer Research 2000, 6, 328.