Stephen R Wedge

Summary

Affiliation: AstraZeneca R and D

Publications

  1. ncbi AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer
    Stephen R Wedge
    Cancer Bioscience, AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom
    Cancer Res 65:4389-400. 2005
  2. ncbi ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration
    Stephen R Wedge
    Department of Cancer and Infection Research, AstraZeneca, Cheshire SK10 4TG, United Kingdom
    Cancer Res 62:4645-55. 2002
  3. doi Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: selective inhibitors of Aurora B kinase with potent anti-tumor activity
    Kevin M Foote
    AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    Bioorg Med Chem Lett 18:1904-9. 2008
  4. ncbi Acute pharmacodynamic and antivascular effects of the vascular endothelial growth factor signaling inhibitor AZD2171 in Calu-6 human lung tumor xenografts
    Neil R Smith
    Cancer Bioscience, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    Mol Cancer Ther 6:2198-208. 2007
  5. doi Inhibition of vascular endothelial growth factor-a signaling induces hypertension: examining the effect of cediranib (recentin; AZD2171) treatment on blood pressure in rat and the use of concomitant antihypertensive therapy
    Jon O Curwen
    Department of Cancer Bioscience, AstraZeneca, Macclesfield, Cheshire, United Kingdom
    Clin Cancer Res 14:3124-31. 2008
  6. doi Examining the acute effects of cediranib (RECENTIN, AZD2171) treatment in tumor models: a dynamic contrast-enhanced MRI study using gadopentate
    Daniel P Bradley
    Department of Enabling Capabilities and Sciences, AstraZeneca, Mereside, Alderley Park, Cheshire, SK10 4TG, UK
    Magn Reson Imaging 27:377-84. 2009
  7. doi Assessing the activity of cediranib, a VEGFR-2/3 tyrosine kinase inhibitor, against VEGFR-1 and members of the structurally related PDGFR family
    Sandra R Brave
    Oncology iMED, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    Mol Cancer Ther 10:861-73. 2011
  8. ncbi AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis
    Robert W Wilkinson
    AstraZeneca Pharmaceuticals, Macclesfield, Cheshire, United Kingdom
    Clin Cancer Res 13:3682-8. 2007
  9. doi An antibody targeted to VEGFR-2 Ig domains 4-7 inhibits VEGFR-2 activation and VEGFR-2-dependent angiogenesis without affecting ligand binding
    Jane Kendrew
    Cancer Bioscience, AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, United Kingdom
    Mol Cancer Ther 10:770-83. 2011
  10. doi Placental growth factor neutralising antibodies give limited anti-angiogenic effects in an in vitro organotypic angiogenesis model
    Sandra R Brave
    Cancer Bioscience, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Angiogenesis 13:337-47. 2010

Collaborators

Detail Information

Publications26

  1. ncbi AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer
    Stephen R Wedge
    Cancer Bioscience, AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom
    Cancer Res 65:4389-400. 2005
    ..AZD2171 is being developed clinically as a once-daily oral therapy for the treatment of cancer...
  2. ncbi ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration
    Stephen R Wedge
    Department of Cancer and Infection Research, AstraZeneca, Cheshire SK10 4TG, United Kingdom
    Cancer Res 62:4645-55. 2002
    ..4 cm(3) volume. ZD6474 is currently in Phase I clinical development as a once-daily oral therapy in patients with advanced cancer...
  3. doi Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: selective inhibitors of Aurora B kinase with potent anti-tumor activity
    Kevin M Foote
    AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    Bioorg Med Chem Lett 18:1904-9. 2008
    ..The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume...
  4. ncbi Acute pharmacodynamic and antivascular effects of the vascular endothelial growth factor signaling inhibitor AZD2171 in Calu-6 human lung tumor xenografts
    Neil R Smith
    Cancer Bioscience, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    Mol Cancer Ther 6:2198-208. 2007
    ..In addition, this work highlights the utility of measuring either pY1175/1173 or pY1214/1212 on VEGFR-2 as a pharmacodynamic marker of VEGFR-2 activation...
  5. doi Inhibition of vascular endothelial growth factor-a signaling induces hypertension: examining the effect of cediranib (recentin; AZD2171) treatment on blood pressure in rat and the use of concomitant antihypertensive therapy
    Jon O Curwen
    Department of Cancer Bioscience, AstraZeneca, Macclesfield, Cheshire, United Kingdom
    Clin Cancer Res 14:3124-31. 2008
    ..We examined the effect of cediranib, a highly potent VEGF signaling inhibitor, on the blood pressure of rats and the ability of standard antihypertensive agents to modulate the consequences of VEGF signaling inhibition...
  6. doi Examining the acute effects of cediranib (RECENTIN, AZD2171) treatment in tumor models: a dynamic contrast-enhanced MRI study using gadopentate
    Daniel P Bradley
    Department of Enabling Capabilities and Sciences, AstraZeneca, Mereside, Alderley Park, Cheshire, SK10 4TG, UK
    Magn Reson Imaging 27:377-84. 2009
    ..05) in both tumor models and iAUC by 23% (P>.05) and 33% (P>.005) in Lovo and C6, respectively. This is the first preclinical investigation to examine the effect of cediranib treatment on tumors by DCE-MRI with gadopentate...
  7. doi Assessing the activity of cediranib, a VEGFR-2/3 tyrosine kinase inhibitor, against VEGFR-1 and members of the structurally related PDGFR family
    Sandra R Brave
    Oncology iMED, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    Mol Cancer Ther 10:861-73. 2011
    ..Collectively, these data indicate that cediranib is a potent pan-VEGFR kinase inhibitor with similar activity against c-Kit but is significantly less potent than PDGFR-α and PDGFR-β...
  8. ncbi AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis
    Robert W Wilkinson
    AstraZeneca Pharmaceuticals, Macclesfield, Cheshire, United Kingdom
    Clin Cancer Res 13:3682-8. 2007
    ..In the current study, we examined the in vivo effects of AZD1152, a novel and specific inhibitor of Aurora kinase activity (with selectivity for Aurora B)...
  9. doi An antibody targeted to VEGFR-2 Ig domains 4-7 inhibits VEGFR-2 activation and VEGFR-2-dependent angiogenesis without affecting ligand binding
    Jane Kendrew
    Cancer Bioscience, AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, United Kingdom
    Mol Cancer Ther 10:770-83. 2011
    ..These data show targeting VEGFR-2 outside of the ligand binding domain results in potent inhibition of VEGFR-2 signaling and inhibition of angiogenesis in vitro and in vivo...
  10. doi Placental growth factor neutralising antibodies give limited anti-angiogenic effects in an in vitro organotypic angiogenesis model
    Sandra R Brave
    Cancer Bioscience, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Angiogenesis 13:337-47. 2010
    ..Such data questions whether neutralising PlGF would have a therapeutic benefit in vivo in the presence of pathological concentrations of VEGF-A...
  11. ncbi Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase
    Andrew A Mortlock
    AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    J Med Chem 50:2213-24. 2007
    ..The compounds display striking in vivo activity, and compound 5 (AZD1152) has been selected for clinical evaluation and is currently in phase 1 clinical trials...
  12. ncbi Dynamic contrast-enhanced MRI of vascular changes induced by the VEGF-signalling inhibitor ZD4190 in human tumour xenografts
    David Checkley
    Enabling Science and Technology, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Magn Reson Imaging 21:475-82. 2003
    ..Collectively these studies suggest that DCEMRI using gadopentetate may have potential clinically, for monitoring inhibition of VEGF signaling in solid tumors...
  13. ncbi The use and refinement of rodent models in anti-cancer drug discovery: a review
    Jon O Curwen
    Cancer Bioscience, AstraZeneca, Alderley Park, Macclesfield, UK
    Altern Lab Anim 37:173-80. 2009
    ..The changes in the UK guidelines on the use of rodents in preclinical cancer testing are also used as an illustration of the progressive refinement in tumour models and drug testing...
  14. ncbi Novel 4-anilinoquinazolines with C-7 basic side chains: design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors
    Laurent F Hennequin
    AstraZeneca, Centre de Recherches, Z I la Pompelle, B P 1050, Chemin de Vrilly, 51689 Reims, Cedex 2, France
    J Med Chem 45:1300-12. 2002
    ..001, Mann Whitney rank sum test), and substantial inhibition (36%, P < 0.02) was evident with 12.5 mg/kg/day...
  15. ncbi Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B kinase inhibitors
    Frederic H Jung
    AstraZeneca, Centre de Recherches, Parc Industriel Pompelle, BP1050, Chemin de Vrilly, 51689 Reims Cedex 2, France
    J Med Chem 49:955-70. 2006
    ....
  16. doi Expression of stromal genes associated with the angiogenic response are not differentiated between human tumour xenografts with divergent vascular morphologies
    Matthew Farren
    Oncology iMED, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK
    Angiogenesis 15:555-68. 2012
    ..The data indicate that although the angiogenic response to the tumour results in reproducible stromal architectures, these responses are not differentiated at the level of gene expression...
  17. pmc AZD3514: A Small Molecule That Modulates Androgen Receptor Signaling and Function In Vitro and In Vivo
    Sarah A Loddick
    Corresponding Author A Nigel Brooks, Oncology iMED, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom
    Mol Cancer Ther 12:1715-27. 2013
    ..Furthermore, this class of compound showed antitumor activity in the HID28 mouse model of CRPC in vivo. AZD3514 is currently in phase I clinical evaluation. Mol Cancer Ther; 12(9); 1715-27. ©2013 AACR. ..
  18. doi The clinical development of molecularly targeted agents in combination with radiation therapy: a pharmaceutical perspective
    Ozlem U Ataman
    Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom Electronic address
    Int J Radiat Oncol Biol Phys 84:e447-54. 2012
    ..Collectively, this analysis suggests that such trials are not given priority by pharmaceutical companies. The potential reasons for this and some challenges and possible solutions are discussed...
  19. ncbi Complete structure of an increasing capillary permeability protein (ICPP) purified from Vipera lebetina venom. ICPP is angiogenic via vascular endothelial growth factor receptor signalling
    Ammar Gasmi
    Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, B P 74, 1002 Tunis Belvedere, Tunisia
    J Biol Chem 277:29992-8. 2002
    ..Therefore, we conclude that this venom-derived ICPP exerts its biological action (permeability and angiogenesis) through activation of VEGF receptor signaling (VEGF-R2 and possibly VEGF-R1)...
  20. ncbi ZD6474, a potent inhibitor of vascular endothelial growth factor signaling, combined with radiotherapy: schedule-dependent enhancement of antitumor activity
    Kaye J Williams
    School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, United Kingdom
    Clin Cancer Res 10:8587-93. 2004
    ..This study was designed to determine the efficacy of combining ZD6474 and radiotherapy in vivo...
  21. ncbi Combination antiangiogenic and androgen deprivation therapy for prostate cancer: a promising therapeutic approach
    Brian Nicholson
    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA
    Clin Cancer Res 10:8728-34. 2004
    ..We examined combined androgen ablation and inhibition of VEGF signaling in an androgen-sensitive human prostate cancer xenograft model (LNCaP) that is known to develop androgen-independent growth after androgen ablation...
  22. ncbi ZD6474, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, inhibits growth of experimental lung metastasis and production of malignant pleural effusions in a non-small cell lung cancer model
    Yuka Matsumori
    Department of Internal Medicine and Molecular Therapeutics, University of Tokushima School of Medicine, Tokushima, 3 18 15 Kuramoto cho, Tokushima, Japan
    Oncol Res 16:15-26. 2006
    ..These results indicate that ZD6474, an inhibitor of VEGFR-2, may be useful in controlling the growth of established lung metastasis and pleural effusions by NSCLC...
  23. doi The tyrosine kinase inhibitor cediranib blocks ligand-induced vascular endothelial growth factor receptor-3 activity and lymphangiogenesis
    Caroline A Heckman
    Molecular Cancer Biology Laboratory, Biomedicum Helsinki and Ludwig Institute for Cancer Research, University of Helsinki, Helsinki, Finland
    Cancer Res 68:4754-62. 2008
    ..Cediranib may, therefore, be an effective means of preventing tumor progression, not only by inhibiting VEGFR-2 activity and angiogenesis, but also by concomitantly inhibiting VEGFR-3 activity and lymphangiogenesis...
  24. ncbi Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit
    Kaye J Williams
    Department of Pharmacy, University of Manchester, Coupland Street, Manchester M13 9PL, United Kingdom
    Mol Cancer Ther 6:599-606. 2007
    ..Collectively, these data support the clinical development of AZD2171 in combination with radiotherapy...
  25. ncbi Antiangiogenic and antitumor activity of a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor ZD6474 in a metastatic human pancreatic tumor model
    Claudius Conrad
    Department of Surgery, University of Munich Grosshadern LMU, Munich, Germany
    Anticancer Drugs 18:569-79. 2007
    ..ZD6474 decreased primary pancreatic tumor growth and reduced lymph node and liver metastases compared with controls or gemcitabine alone. Tumor growth was inhibited further in animals receiving ZD6474 and gemcitabine in combination...
  26. doi Dual inhibition of VEGFR and EGFR signaling reduces the incidence and size of intestinal adenomas in Apc(Min/+) mice
    Denis Alferez
    Cancer Research UK, Histopathology Unit, London Research Institute, London, UK
    Mol Cancer Ther 7:590-8. 2008
    ..Therefore, targeting both VEGFR- and EGFR-dependent signaling may be a beneficial strategy in early intestinal cancer...