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Identification of a novel orally bioavailable ERK5 inhibitor with selectivity over p38α and BRD4.

Myers SM, Miller DC, Molyneux L, Arasta M, Bawn RH, Blackburn TJ, Cook SJ, Edwards N, Endicott JA, Golding BT, Griffin RJ, Hammonds T, Hardcastle IR, Harnor SJ, Heptinstall AB, Lochhead PA, Martin MP, Martin NC, Newell DR, Owen PJ, Pang LC, Reuillon T, Rigoreau LJM, Thomas HD, Tucker JA, Wang LZ, Wong AC, Noble MEM, Wedge SR, Cano C.

Eur J Med Chem. 2019 Sep 15;178:530-543. doi: 10.1016/j.ejmech.2019.05.057. Epub 2019 May 25.


Development of a fluorescence-based cellular apoptosis reporter.

Balderstone LA, Dawson JC, Welman A, Serrels A, Wedge SR, Brunton VG.

Methods Appl Fluoresc. 2018 Oct 24;7(1):015001. doi: 10.1088/2050-6120/aae6f8.


Highly Potent Clickable Probe for Cellular Imaging of MDM2 and Assessing Dynamic Responses to MDM2-p53 Inhibition.

Lebraud H, Noble RA, Phillips N, Heam K, Castro J, Zhao Y, Newell DR, Lunec J, Wedge SR, Heightman TD.

Bioconjug Chem. 2018 Jun 20;29(6):2100-2106. doi: 10.1021/acs.bioconjchem.8b00315. Epub 2018 Jun 12.


Identification of a novel ligand for the ATAD2 bromodomain with selectivity over BRD4 through a fragment growing approach.

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.

Org Biomol Chem. 2018 Mar 14;16(11):1843-1850. doi: 10.1039/c8ob00099a.


Differential Regulation of G1 CDK Complexes by the Hsp90-Cdc37 Chaperone System.

Hallett ST, Pastok MW, Morgan RML, Wittner A, Blundell KLIM, Felletar I, Wedge SR, Prodromou C, Noble MEM, Pearl LH, Endicott JA.

Cell Rep. 2017 Oct 31;21(5):1386-1398. doi: 10.1016/j.celrep.2017.10.042.


Ex vivo treatment of patient biopsies as a novel method to assess colorectal tumour response to the MEK1/2 inhibitor, Selumetinib.

Novo SM, Wedge SR, Stark LA.

Sci Rep. 2017 Sep 20;7(1):12020. doi: 10.1038/s41598-017-12222-9.


Inhibition of monocarboxyate transporter 1 by AZD3965 as a novel therapeutic approach for diffuse large B-cell lymphoma and Burkitt lymphoma.

Noble RA, Bell N, Blair H, Sikka A, Thomas H, Phillips N, Nakjang S, Miwa S, Crossland R, Rand V, Televantou D, Long A, Keun HC, Bacon CM, Bomken S, Critchlow SE, Wedge SR.

Haematologica. 2017 Jul;102(7):1247-1257. doi: 10.3324/haematol.2016.163030. Epub 2017 Apr 6.


A minimum core outcome dataset for the reporting of preclinical chemotherapeutic drug studies: Lessons learned from multiple discordant methodologies in the setting of colorectal cancer.

West MA, Roman A, Sayan E, Primrose JN, Wedge SR, Underwood TJ, Mirnezami AH.

Crit Rev Oncol Hematol. 2017 Apr;112:80-102. doi: 10.1016/j.critrevonc.2017.02.008. Epub 2017 Feb 16. Review.


Aurora A regulates expression of AR-V7 in models of castrate resistant prostate cancer.

Jones D, Noble M, Wedge SR, Robson CN, Gaughan L.

Sci Rep. 2017 Feb 16;7:40957. doi: 10.1038/srep40957.


Cyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines.

Coxon CR, Anscombe E, Harnor SJ, Martin MP, Carbain B, Golding BT, Hardcastle IR, Harlow LK, Korolchuk S, Matheson CJ, Newell DR, Noble ME, Sivaprakasam M, Tudhope SJ, Turner DM, Wang LZ, Wedge SR, Wong C, Griffin RJ, Endicott JA, Cano C.

J Med Chem. 2017 Mar 9;60(5):1746-1767. doi: 10.1021/acs.jmedchem.6b01254. Epub 2017 Feb 14.


Clinical development of new drug-radiotherapy combinations.

Sharma RA, Plummer R, Stock JK, Greenhalgh TA, Ataman O, Kelly S, Clay R, Adams RA, Baird RD, Billingham L, Brown SR, Buckland S, Bulbeck H, Chalmers AJ, Clack G, Cranston AN, Damstrup L, Ferraldeschi R, Forster MD, Golec J, Hagan RM, Hall E, Hanauske AR, Harrington KJ, Haswell T, Hawkins MA, Illidge T, Jones H, Kennedy AS, McDonald F, Melcher T, O'Connor JP, Pollard JR, Saunders MP, Sebag-Montefiore D, Smitt M, Staffurth J, Stratford IJ, Wedge SR; NCRI CTRad Academia-Pharma Joint Working Group.

Nat Rev Clin Oncol. 2016 Oct;13(10):627-42. doi: 10.1038/nrclinonc.2016.79. Epub 2016 Jun 1.


Tumor cells with KRAS or BRAF mutations or ERK5/MAPK7 amplification are not addicted to ERK5 activity for cell proliferation.

Lochhead PA, Clark J, Wang LZ, Gilmour L, Squires M, Gilley R, Foxton C, Newell DR, Wedge SR, Cook SJ.

Cell Cycle. 2016;15(4):506-18. doi: 10.1080/15384101.2015.1120915.


Capturing complex tumour biology in vitro: histological and molecular characterisation of precision cut slices.

Davies EJ, Dong M, Gutekunst M, Närhi K, van Zoggel HJ, Blom S, Nagaraj A, Metsalu T, Oswald E, Erkens-Schulze S, Delgado San Martin JA, Turkki R, Wedge SR, af Hällström TM, Schueler J, van Weerden WM, Verschuren EW, Barry ST, van der Kuip H, Hickman JA.

Sci Rep. 2015 Dec 9;5:17187. doi: 10.1038/srep17187.


PDGFR Inhibition Results in Pericyte Depletion and Hemorrhage into the Corpus Luteum of the Rat Ovary.

Hall AP, Ashton S, Horner J, Wilson Z, Reens J, Richmond GH, Barry ST, Wedge SR.

Toxicol Pathol. 2016 Jan;44(1):98-111. doi: 10.1177/0192623315613452. Epub 2015 Nov 3.


Identification and Characterization of an Irreversible Inhibitor of CDK2.

Anscombe E, Meschini E, Mora-Vidal R, Martin MP, Staunton D, Geitmann M, Danielson UH, Stanley WA, Wang LZ, Reuillon T, Golding BT, Cano C, Newell DR, Noble ME, Wedge SR, Endicott JA, Griffin RJ.

Chem Biol. 2015 Sep 17;22(9):1159-64. doi: 10.1016/j.chembiol.2015.07.018. Epub 2015 Aug 27.


Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy.

O'Neill D, Jones D, Wade M, Grey J, Nakjang S, Guo W, Cork D, Davies BR, Wedge SR, Robson CN, Gaughan L.

Oncotarget. 2015 Sep 22;6(28):26029-40. doi: 10.18632/oncotarget.4347.


Mechanisms that influence tumour response to VEGF-pathway inhibitors.

Smith NR, Wedge SR, Pommier A, Barry ST.

Biochem Soc Trans. 2014 Dec;42(6):1601-7. doi: 10.1042/BST20140261. Review.


Inhibition of PI3Kβ signaling with AZD8186 inhibits growth of PTEN-deficient breast and prostate tumors alone and in combination with docetaxel.

Hancox U, Cosulich S, Hanson L, Trigwell C, Lenaghan C, Ellston R, Dry H, Crafter C, Barlaam B, Fitzek M, Smith PD, Ogilvie D, D'Cruz C, Castriotta L, Wedge SR, Ward L, Powell S, Lawson M, Davies BR, Harrington EA, Foster E, Cumberbatch M, Green S, Barry ST.

Mol Cancer Ther. 2015 Jan;14(1):48-58. doi: 10.1158/1535-7163.MCT-14-0406. Epub 2014 Nov 14.


Tumor stromal phenotypes define VEGF sensitivity--response.

Smith NR, Baker D, Farren M, Pommier A, Swann R, Wang X, Mistry S, McDaid K, Kendrew J, Womack C, Wedge SR, Barry ST.

Clin Cancer Res. 2014 Oct 1;20(19):5141. doi: 10.1158/1078-0432.CCR-14-0681. No abstract available.


Examining changes in [18 F]FDG and [18 F]FLT uptake in U87-MG glioma xenografts as early response biomarkers to treatment with the dual mTOR1/2 inhibitor AZD8055.

Keen HG, Ricketts SA, Maynard J, Logie A, Odedra R, Shannon AM, Wedge SR, Guichard SM.

Mol Imaging Biol. 2014 Jun;16(3):421-30. doi: 10.1007/s11307-013-0705-0.


Tumor stromal architecture can define the intrinsic tumor response to VEGF-targeted therapy.

Smith NR, Baker D, Farren M, Pommier A, Swann R, Wang X, Mistry S, McDaid K, Kendrew J, Womack C, Wedge SR, Barry ST.

Clin Cancer Res. 2013 Dec 15;19(24):6943-56. doi: 10.1158/1078-0432.CCR-13-1637. Epub 2013 Sep 12.


AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo.

Loddick SA, Ross SJ, Thomason AG, Robinson DM, Walker GE, Dunkley TP, Brave SR, Broadbent N, Stratton NC, Trueman D, Mouchet E, Shaheen FS, Jacobs VN, Cumberbatch M, Wilson J, Jones RD, Bradbury RH, Rabow A, Gaughan L, Womack C, Barry ST, Robson CN, Critchlow SE, Wedge SR, Brooks AN.

Mol Cancer Ther. 2013 Sep;12(9):1715-27. doi: 10.1158/1535-7163.MCT-12-1174. Epub 2013 Jul 16.


Anti-tumour and anti-vascular effects of cediranib (AZD2171) alone and in combination with other anti-tumour therapies.

Kendrew J, Odedra R, Logié A, Taylor PJ, Pearsall S, Ogilvie DJ, Wedge SR, Jürgensmeier JM.

Cancer Chemother Pharmacol. 2013 Apr;71(4):1021-32. doi: 10.1007/s00280-013-2097-x. Epub 2013 Jan 26.


Inhibition of Aurora-B kinase activity confers antitumor efficacy in preclinical mouse models of early and advanced gastrointestinal neoplasia.

Alferez DG, Goodlad RA, Odedra R, Sini P, Crafter C, Ryan AJ, Wedge SR, Wright NA, Anderson E, Wilkinson RW.

Int J Oncol. 2012 Oct;41(4):1475-85. doi: 10.3892/ijo.2012.1580. Epub 2012 Jul 31.


The clinical development of molecularly targeted agents in combination with radiation therapy: a pharmaceutical perspective.

Ataman OU, Sambrook SJ, Wilks C, Lloyd A, Taylor AE, Wedge SR.

Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e447-54. doi: 10.1016/j.ijrobp.2012.05.019. Epub 2012 Jul 20. Review.


Expression of stromal genes associated with the angiogenic response are not differentiated between human tumour xenografts with divergent vascular morphologies.

Farren M, Weston S, Brown H, Broadbent N, Powell S, Shaw R, Smith NR, Inglis R, Graham A, Ashton S, Wedge SR, Barry ST.

Angiogenesis. 2012 Dec;15(4):555-68. doi: 10.1007/s10456-012-9280-2. Epub 2012 May 27.


Inhibition of PARP-1 by olaparib (AZD2281) increases the radiosensitivity of a lung tumor xenograft.

Senra JM, Telfer BA, Cherry KE, McCrudden CM, Hirst DG, O'Connor MJ, Wedge SR, Stratford IJ.

Mol Cancer Ther. 2011 Oct;10(10):1949-58. doi: 10.1158/1535-7163.MCT-11-0278. Epub 2011 Aug 8.


An evaluation of 2-deoxy-2-[18F]fluoro-D-glucose and 3'-deoxy-3'-[18F]-fluorothymidine uptake in human tumor xenograft models.

Keen H, Pichler B, Kukuk D, Duchamp O, Raguin O, Shannon A, Whalley N, Jacobs V, Bales J, Gingles N, Ricketts SA, Wedge SR.

Mol Imaging Biol. 2012 Jun;14(3):355-65. doi: 10.1007/s11307-011-0504-4.


Assessing the activity of cediranib, a VEGFR-2/3 tyrosine kinase inhibitor, against VEGFR-1 and members of the structurally related PDGFR family.

Brave SR, Ratcliffe K, Wilson Z, James NH, Ashton S, Wainwright A, Kendrew J, Dudley P, Broadbent N, Sproat G, Taylor S, Barnes C, Silva JC, Farnsworth CL, Hennequin L, Ogilvie DJ, Jürgensmeier JM, Shibuya M, Wedge SR, Barry ST.

Mol Cancer Ther. 2011 May;10(5):861-73. doi: 10.1158/1535-7163.MCT-10-0976. Epub 2011 Mar 25.


An antibody targeted to VEGFR-2 Ig domains 4-7 inhibits VEGFR-2 activation and VEGFR-2-dependent angiogenesis without affecting ligand binding.

Kendrew J, Eberlein C, Hedberg B, McDaid K, Smith NR, Weir HM, Wedge SR, Blakey DC, Foltz I, Zhou J, Kang JS, Barry ST.

Mol Cancer Ther. 2011 May;10(5):770-83. doi: 10.1158/1535-7163.MCT-10-0876. Epub 2011 Mar 9.


Placental growth factor neutralising antibodies give limited anti-angiogenic effects in an in vitro organotypic angiogenesis model.

Brave SR, Eberlein C, Shibuya M, Wedge SR, Barry ST.

Angiogenesis. 2010 Dec;13(4):337-47. doi: 10.1007/s10456-010-9190-0. Epub 2010 Oct 16.


Guidelines for the welfare and use of animals in cancer research.

Workman P, Aboagye EO, Balkwill F, Balmain A, Bruder G, Chaplin DJ, Double JA, Everitt J, Farningham DA, Glennie MJ, Kelland LR, Robinson V, Stratford IJ, Tozer GM, Watson S, Wedge SR, Eccles SA; Committee of the National Cancer Research Institute.

Br J Cancer. 2010 May 25;102(11):1555-77. doi: 10.1038/sj.bjc.6605642.


The mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) enhances the radiation responsiveness of lung and colorectal tumor xenografts.

Shannon AM, Telfer BA, Smith PD, Babur M, Logie A, Wilkinson RW, Debray C, Stratford IJ, Williams KJ, Wedge SR.

Clin Cancer Res. 2009 Nov 1;15(21):6619-29. doi: 10.1158/1078-0432.CCR-08-2958. Epub 2009 Oct 20.


The use and refinement of rodent models in anti-cancer drug discovery: a review.

Curwen JO, Wedge SR.

Altern Lab Anim. 2009 Apr;37(2):173-80. Review.


The kinase inhibitor O6-cyclohexylmethylguanine (NU2058) potentiates the cytotoxicity of cisplatin by mechanisms that are independent of its effect upon CDK2.

Harrison LR, Ottley CJ, Pearson DG, Roche C, Wedge SR, Dolan ME, Newell DR, Tilby MJ.

Biochem Pharmacol. 2009 May 15;77(10):1586-92. doi: 10.1016/j.bcp.2009.02.018. Epub 2009 Mar 5.


Use of a novel Arg-Gly-Asp radioligand, 18F-AH111585, to determine changes in tumor vascularity after antitumor therapy.

Morrison MS, Ricketts SA, Barnett J, Cuthbertson A, Tessier J, Wedge SR.

J Nucl Med. 2009 Jan;50(1):116-22. doi: 10.2967/jnumed.108.056077. Epub 2008 Dec 17.


Inhibition of vascular endothelial growth factor signalling using cediranib (RECENTIN; AZD2171) enhances radiation response and causes substantial physiological changes in lung tumour xenografts.

Williams KJ, Telfer BA, Shannon AM, Babur M, Stratford IJ, Wedge SR.

Br J Radiol. 2008 Oct;81 Spec No 1:S21-7. doi: 10.1259/bjr/59853976.


Examining the acute effects of cediranib (RECENTIN, AZD2171) treatment in tumor models: a dynamic contrast-enhanced MRI study using gadopentate.

Bradley DP, Tessier JJ, Lacey T, Scott M, Jürgensmeier JM, Odedra R, Mills J, Kilburn L, Wedge SR.

Magn Reson Imaging. 2009 Apr;27(3):377-84. doi: 10.1016/j.mri.2008.07.021. Epub 2008 Sep 23.


The tyrosine kinase inhibitor cediranib blocks ligand-induced vascular endothelial growth factor receptor-3 activity and lymphangiogenesis.

Heckman CA, Holopainen T, Wirzenius M, Keskitalo S, Jeltsch M, Ylä-Herttuala S, Wedge SR, Jürgensmeier JM, Alitalo K.

Cancer Res. 2008 Jun 15;68(12):4754-62. doi: 10.1158/0008-5472.CAN-07-5809.


Dual inhibition of VEGFR and EGFR signaling reduces the incidence and size of intestinal adenomas in Apc(Min/+) mice.

Alferez D, Wilkinson RW, Watkins J, Poulsom R, Mandir N, Wedge SR, Pyrah IT, Smith NR, Jackson L, Ryan AJ, Goodlad RA.

Mol Cancer Ther. 2008 Mar;7(3):590-8. doi: 10.1158/1535-7163.MCT-07-0433.


Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: selective inhibitors of Aurora B kinase with potent anti-tumor activity.

Foote KM, Mortlock AA, Heron NM, Jung FH, Hill GB, Pasquet G, Brady MC, Green S, Heaton SP, Kearney S, Keen NJ, Odedra R, Wedge SR, Wilkinson RW.

Bioorg Med Chem Lett. 2008 Mar 15;18(6):1904-9. doi: 10.1016/j.bmcl.2008.02.002. Epub 2008 Feb 7.


Acute pharmacodynamic and antivascular effects of the vascular endothelial growth factor signaling inhibitor AZD2171 in Calu-6 human lung tumor xenografts.

Smith NR, James NH, Oakley I, Wainwright A, Copley C, Kendrew J, Womersley LM, Jürgensmeier JM, Wedge SR, Barry ST.

Mol Cancer Ther. 2007 Aug;6(8):2198-208.


AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis.

Wilkinson RW, Odedra R, Heaton SP, Wedge SR, Keen NJ, Crafter C, Foster JR, Brady MC, Bigley A, Brown E, Byth KF, Barrass NC, Mundt KE, Foote KM, Heron NM, Jung FH, Mortlock AA, Boyle FT, Green S.

Clin Cancer Res. 2007 Jun 15;13(12):3682-8.


Effects of AZD2171 and vandetanib (ZD6474, Zactima) on haemodynamic variables in an SW620 human colon tumour model: an investigation using dynamic contrast-enhanced MRI and the rapid clearance blood pool contrast agent, P792 (gadomelitol).

Bradley DP, Tessier JL, Checkley D, Kuribayashi H, Waterton JC, Kendrew J, Wedge SR.

NMR Biomed. 2008 Jan;21(1):42-52. Erratum in: NMR Biomed. 2008 Mar;21(3):302.


Antiangiogenic and antitumor activity of a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor ZD6474 in a metastatic human pancreatic tumor model.

Conrad C, Ischenko I, Köhl G, Wiegand U, Guba M, Yezhelyev M, Ryan AJ, Barge A, Geissler EK, Wedge SR, Jauch KW, Bruns CJ.

Anticancer Drugs. 2007 Jun;18(5):569-79.


Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase.

Mortlock AA, Foote KM, Heron NM, Jung FH, Pasquet G, Lohmann JJ, Warin N, Renaud F, De Savi C, Roberts NJ, Johnson T, Dousson CB, Hill GB, Perkins D, Hatter G, Wilkinson RW, Wedge SR, Heaton SP, Odedra R, Keen NJ, Crafter C, Brown E, Thompson K, Brightwell S, Khatri L, Brady MC, Kearney S, McKillop D, Rhead S, Parry T, Green S.

J Med Chem. 2007 May 3;50(9):2213-24. Epub 2007 Mar 21.


Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit.

Williams KJ, Telfer BA, Shannon AM, Babur M, Stratford IJ, Wedge SR.

Mol Cancer Ther. 2007 Feb;6(2):599-606.


Inhibiting vascular endothelial growth factor receptor-2 signaling reduces tumor burden in the ApcMin/+ mouse model of early intestinal cancer.

Goodlad RA, Ryan AJ, Wedge SR, Pyrah IT, Alferez D, Poulsom R, Smith NR, Mandir N, Watkins AJ, Wilkinson RW.

Carcinogenesis. 2006 Oct;27(10):2133-9. Epub 2006 Jun 16.


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