Caroline J Springer

Summary

Affiliation: Institute of Cancer Research
Country: UK

Publications

  1. doi request reprint BRAF as a therapeutic target: a patent review (2006 - 2012)
    Alfonso Zambon
    The Institute of Cancer Research, Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    Expert Opin Ther Pat 23:155-64. 2013
  2. doi request reprint Novel hinge binder improves activity and pharmacokinetic properties of BRAF inhibitors
    Alfonso Zambon
    The Institute of Cancer Research, Cancer Research UK Centre for Cancer Therapeutics, Sutton, Surrey, UK
    J Med Chem 53:5639-55. 2010
  3. doi request reprint BRAF inhibitors based on an imidazo[4,5]pyridin-2-one scaffold and a meta substituted middle ring
    Arnaud Nourry
    Cancer Research UK Centre of Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    J Med Chem 53:1964-78. 2010
  4. doi request reprint Pyridoimidazolones as novel potent inhibitors of v-Raf murine sarcoma viral oncogene homologue B1 (BRAF)
    Dan Niculescu-Duvaz
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    J Med Chem 52:2255-64. 2009
  5. doi request reprint Development of novel, highly potent inhibitors of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF): increasing cellular potency through optimization of a distal heteroaromatic group
    Bart M J M Suijkerbuijk
    The Institute of Cancer Research, Cancer Research UK Centre for Cancer Therapeutics, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    J Med Chem 53:2741-56. 2010
  6. doi request reprint Attenuated Salmonella targets prodrug activating enzyme carboxypeptidase G2 to mouse melanoma and human breast and colon carcinomas for effective suicide gene therapy
    Frank Friedlos
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Clin Cancer Res 14:4259-66. 2008
  7. doi request reprint Novel inhibitors of the v-raf murine sarcoma viral oncogene homologue B1 (BRAF) based on a 2,6-disubstituted pyrazine scaffold
    Ion Niculescu-Duvaz
    The Institute of Cancer Research, Cancer Research UK Centre for Cancer Therapeutics, Sutton, Surrey, UK
    J Med Chem 51:3261-74. 2008
  8. pmc Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds
    Dan Niculescu-Duvaz
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    Bioorg Med Chem 18:6934-52. 2010
  9. ncbi request reprint Novel fluorinated prodrugs for activation by carboxypeptidase G2 showing good in vivo antitumor activity in gene-directed enzyme prodrug therapy
    Lawrence C Davies
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    J Med Chem 48:5321-8. 2005
  10. doi request reprint Inducible expression of (V600E) Braf using tyrosinase-driven Cre recombinase results in embryonic lethality
    Nathalie Dhomen
    The Institute of Cancer Research, Signal Transduction Team, Cancer Research UK Centre for Cell and Molecular Biology, London, UK
    Pigment Cell Melanoma Res 23:112-20. 2010

Collaborators

  • Ion Niculescu-Duvaz
  • Martin O Leach
  • Geoffrey S Payne
  • Florence I Raynaud
  • Simon P Robinson
  • Silke Schepelmann
  • Antonio Chiloeches
  • Veronique Delmas
  • C Michael Jones
  • Harmen P Dijkstra
  • Lionel Larue
  • Jorge S Reis-Filho
  • Laura Mancini
  • David Barford
  • Dan Niculescu-Duvaz
  • Richard Marais
  • Alfonso Zambon
  • Frank Friedlos
  • Lawrence Davies
  • Bart M J M Suijkerbuijk
  • Steven Whittaker
  • Delphine Ménard
  • Arnaud Nourry
  • Douglas Hedley
  • Ruth Kirk
  • Helen A Manne
  • Lesley Ogilvie
  • Yann Jamin
  • Lesley M Ogilvie
  • Jan Martin
  • Nathalie Dhomen
  • Catherine Gaulon
  • Ian Scanlon
  • Panos Lehouritis
  • Jean Francois Pons
  • Thomas R Eykyn
  • Lynette Smyth
  • Catrin Pritchard
  • Sonja J Heidorn
  • Filipa Lopes
  • Javier Moreno-Farre
  • Richard D Taylor
  • Adrian Gill
  • Robert Hayward
  • Lawrence C Davies
  • Maria Karasarides
  • Christopher J Marshall
  • Paul T C Wan
  • Evon S C Poon
  • Silvy da Rocha Dias
  • Andrew K Takle
  • Jahan Hussain
  • Carla Milagre
  • Tom Coulter
  • Natasha Preece
  • Natasha P U Preece
  • Ion Niculescu-Duvas
  • David M Wilson
  • Neus Cantarino
  • Afshan McCarthy
  • Deborah Henderson
  • Helen Manne
  • Cristina Gabellieri
  • Steven Reynolds
  • Esteban Roman
  • David Bermudes
  • Ivan King
  • Jayne Getaz
  • Ian J Scanlon
  • Valerie M Good
  • S Mark Roe
  • Mathew J Garnett
  • Sharlene Lee
  • James Heyes
  • Stephen M Stribbling
  • Janet Martin
  • Robert A Spooner

Detail Information

Publications30

  1. doi request reprint BRAF as a therapeutic target: a patent review (2006 - 2012)
    Alfonso Zambon
    The Institute of Cancer Research, Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    Expert Opin Ther Pat 23:155-64. 2013
    ..Some of the drugs thus developed, such as vemurafenib and dabrafenib, show impressive responses in melanoma patients harbouring a BRAF mutation...
  2. doi request reprint Novel hinge binder improves activity and pharmacokinetic properties of BRAF inhibitors
    Alfonso Zambon
    The Institute of Cancer Research, Cancer Research UK Centre for Cancer Therapeutics, Sutton, Surrey, UK
    J Med Chem 53:5639-55. 2010
    ..These compounds display optimal pharmacokinetic properties that warrant further in vivo investigations...
  3. doi request reprint BRAF inhibitors based on an imidazo[4,5]pyridin-2-one scaffold and a meta substituted middle ring
    Arnaud Nourry
    Cancer Research UK Centre of Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    J Med Chem 53:1964-78. 2010
    ....
  4. doi request reprint Pyridoimidazolones as novel potent inhibitors of v-Raf murine sarcoma viral oncogene homologue B1 (BRAF)
    Dan Niculescu-Duvaz
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    J Med Chem 52:2255-64. 2009
    ..These compounds have great potential in the treatment of mutant BRAF melanomas...
  5. doi request reprint Development of novel, highly potent inhibitors of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF): increasing cellular potency through optimization of a distal heteroaromatic group
    Bart M J M Suijkerbuijk
    The Institute of Cancer Research, Cancer Research UK Centre for Cancer Therapeutics, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    J Med Chem 53:2741-56. 2010
    ..Concomitant benefits are good oral bioavailability and high plasma concentrations in vivo...
  6. doi request reprint Attenuated Salmonella targets prodrug activating enzyme carboxypeptidase G2 to mouse melanoma and human breast and colon carcinomas for effective suicide gene therapy
    Frank Friedlos
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Clin Cancer Res 14:4259-66. 2008
    ....
  7. doi request reprint Novel inhibitors of the v-raf murine sarcoma viral oncogene homologue B1 (BRAF) based on a 2,6-disubstituted pyrazine scaffold
    Ion Niculescu-Duvaz
    The Institute of Cancer Research, Cancer Research UK Centre for Cancer Therapeutics, Sutton, Surrey, UK
    J Med Chem 51:3261-74. 2008
    ..Several compounds were identified with IC 50s of 300-500 nM for (V600E)BRAF, and all compounds that were assessed showed selectivity for (V600E)BRAF compared to CRAF by 5-->86-fold...
  8. pmc Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds
    Dan Niculescu-Duvaz
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    Bioorg Med Chem 18:6934-52. 2010
    ....
  9. ncbi request reprint Novel fluorinated prodrugs for activation by carboxypeptidase G2 showing good in vivo antitumor activity in gene-directed enzyme prodrug therapy
    Lawrence C Davies
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    J Med Chem 48:5321-8. 2005
    ....
  10. doi request reprint Inducible expression of (V600E) Braf using tyrosinase-driven Cre recombinase results in embryonic lethality
    Nathalie Dhomen
    The Institute of Cancer Research, Signal Transduction Team, Cancer Research UK Centre for Cell and Molecular Biology, London, UK
    Pigment Cell Melanoma Res 23:112-20. 2010
    ..Our data suggests that the presence of these cells in the organs that are normally occupied by melanocytes leads to severe developmental disruption, resulting in catastrophic defects and leading to death of the individual...
  11. ncbi request reprint Novel inhibitors of B-RAF based on a disubstituted pyrazine scaffold. Generation of a nanomolar lead
    Ion Niculescu-Duvaz
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    J Med Chem 49:407-16. 2006
    ..Their biological profiles against isolated B-RAF and mutated B-RAF in a cellular assay have been determined. These efforts led to the identification of two compounds exhibiting activities lower than 800 nM against B-RAF...
  12. doi request reprint Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring
    Delphine Ménard
    The Institute of Cancer Research, UK Centre for Cancer Therapeutics, Sutton, Surrey SM2 5NG, United Kingdom
    J Med Chem 52:3881-91. 2009
    ..Substitution on the central phenyl ring of a 3-fluoro, a naphthyl, or a 3-thiomethyl group improves activity to yield compounds with an IC(50) of 1 nM for purified (V600E)BRAF and nanomolar activity in cells...
  13. doi request reprint Potent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents
    Dan Niculescu-Duvaz
    The Institute of Cancer Research, Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    Bioorg Med Chem 21:1284-304. 2013
    ....
  14. pmc Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF
    Sonja J Heidorn
    The Institute of Cancer Research, Signal Transduction Team, Section of Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, UK
    Cell 140:209-21. 2010
    ....
  15. ncbi request reprint Self-immolative nitrogen mustards prodrugs cleavable by carboxypeptidase G2 (CPG2) showing large cytotoxicity differentials in GDEPT
    Dan Niculescu-Duvaz
    CR UK Centre for Cancer Therapeutics at the Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    J Med Chem 46:1690-705. 2003
    ..An additional six compounds show better cytotoxicity differential than the published N-[4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl]-l-glutamic acid (CMDA) prodrug...
  16. ncbi request reprint Design of prodrugs for suicide gene therapy
    Dan Niculescu-Duvaz
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK
    Methods Mol Med 90:161-202. 2004
  17. doi request reprint A novel technique to monitor carboxypeptidase G2 expression in suicide gene therapy using 19F magnetic resonance spectroscopy
    Laura Mancini
    Cancer Research UK Clinical Magnetic Resonance Research Group, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK
    NMR Biomed 22:561-6. 2009
    ..The MRS conversion half-life (470 min) agreed with that measured by HPLC (500 min). This substrate is, therefore, suitable for evaluating gene delivery and expression prior to administration of the therapeutic agent...
  18. doi request reprint Small molecule inhibitors of BRAF in clinical trials
    Alfonso Zambon
    The Institute of Cancer Research, Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    Bioorg Med Chem Lett 22:789-92. 2012
    ..Over the last few years, BRAF has emerged as a validated target in melanoma. This review summarises recent advances in the development of BRAF inhibitors, focussing on agents that have been assessed clinically...
  19. ncbi request reprint Viral vectors for gene-directed enzyme prodrug therapy
    Silke Schepelmann
    The Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, Surrey, UK
    Curr Gene Ther 6:647-70. 2006
    ..They include replication-deficient and replication-selective (oncolytic) viruses. Recent advances in engineering viruses for GDEPT are reviewed in this article and data from both preclinical studies and clinical trials are discussed...
  20. doi request reprint Noninvasive detection of carboxypeptidase G2 activity in vivo
    Yann Jamin
    Cancer Research UK and EPRSC Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
    NMR Biomed 24:343-50. 2011
    ..The addition of in vivo reporter probes, such as 3,5-DFBGlu, to the armamentarium of prodrugs cleaved by CPG2 affords new applications for CPG2 as a gene reporter of transgene expression...
  21. ncbi request reprint B-RAF is a therapeutic target in melanoma
    Maria Karasarides
    Signal Transduction Team, The Cancer Research UK Centre for Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    Oncogene 23:6292-8. 2004
    ....
  22. ncbi request reprint Introduction to the background, principles, and state of the art in suicide gene therapy
    Ion Niculescu-Duvaz
    Cancer Research, UK Centre for Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    Mol Biotechnol 30:71-88. 2005
    ..The possible strategies to improve GDEPT are also discussed...
  23. ncbi request reprint Gene regulation in cancer gene therapy strategies
    Ian Scanlon
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    Curr Med Chem 10:2175-84. 2003
    ..A variety of systems have been reported in an ever widening range of applications, this paper describes these systems with specific reference to cancer gene therapy...
  24. doi request reprint Hyperpolarized (13)C magnetic resonance detection of carboxypeptidase G2 activity
    Yann Jamin
    CRUK and EPSRC Cancer Imaging Centre, Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
    Magn Reson Med 62:1300-4. 2009
    ..We discuss the feasibility of translating these experiments to generate metabolic images of CPG2 activity in vivo...
  25. ncbi request reprint Structure-activity relationship in cationic lipid mediated gene transfection
    Dan Niculescu-Duvaz
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    Curr Med Chem 10:1233-61. 2003
    ....
  26. ncbi request reprint Introduction to the background, principles, and state of the art in suicide gene therapy
    Ion Niculescu-Duvaz
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK
    Methods Mol Med 90:1-27. 2004
  27. ncbi request reprint Introduction to vectors for suicide gene therapy
    Caroline J Springer
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK
    Methods Mol Med 90:29-45. 2004
  28. ncbi request reprint Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
    Paul T C Wan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Cell 116:855-67. 2004
    ..The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism...
  29. doi request reprint Long functionalized poly(ethylene glycol)s of defined molecular weight: synthesis and application in solid-phase synthesis of conjugates
    Dan Niculescu-Duvaz
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Bioconjug Chem 19:973-81. 2008
    ..The assembly of the peptide, PEG linker, and targeting group on solid support resulted in the synthesis of a conjugate of defined molecular weight and structure...
  30. ncbi request reprint Three new prodrugs for suicide gene therapy using carboxypeptidase G2 elicit bystander efficacy in two xenograft models
    Frank Friedlos
    Cancer Research Campaign Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, SM2 5NG United Kingdom
    Cancer Res 62:1724-9. 2002
    ....