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Items: 34


High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers.

Anderhub SJ, Mak GW, Gurden MD, Faisal A, Drosopoulos K, Walsh K, Woodward HL, Innocenti P, Westwood IM, Naud S, Hayes A, Theofani E, Filosto S, Saville H, Burke R, van Montfort RLM, Raynaud FI, Blagg J, Hoelder S, Eccles SA, Linardopoulos S.

Mol Cancer Ther. 2019 Oct;18(10):1696-1707. doi: 10.1158/1535-7163.MCT-18-1203.


Introduction of a Methyl Group Curbs Metabolism of Pyrido[3,4- d]pyrimidine Monopolar Spindle 1 (MPS1) Inhibitors and Enables the Discovery of the Phase 1 Clinical Candidate N2-(2-Ethoxy-4-(4-methyl-4 H-1,2,4-triazol-3-yl)phenyl)-6-methyl- N8-neopentylpyrido[3,4- d]pyrimidine-2,8-diamine (BOS172722).

Woodward HL, Innocenti P, Cheung KJ, Hayes A, Roberts J, Henley AT, Faisal A, Mak GW, Box G, Westwood IM, Cronin N, Carter M, Valenti M, De Haven Brandon A, O'Fee L, Saville H, Schmitt J, Burke R, Broccatelli F, van Montfort RLM, Raynaud FI, Eccles SA, Linardopoulos S, Blagg J, Hoelder S.

J Med Chem. 2018 Sep 27;61(18):8226-8240. doi: 10.1021/acs.jmedchem.8b00690. Epub 2018 Sep 10.


Synthesis and profiling of a 3-aminopyridin-2-one-based kinase targeted fragment library: Identification of 3-amino-5-(pyridin-4-yl)pyridin-2(1H)-one scaffold for monopolar spindle 1 (MPS1) and Aurora kinases inhibition.

Fearon D, Westwood IM, van Montfort RLM, Bayliss R, Jones K, Bavetsias V.

Bioorg Med Chem. 2018 Jul 15;26(11):3021-3029. doi: 10.1016/j.bmc.2018.04.033. Epub 2018 Apr 17.


Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.

Faisal A, Mak GWY, Gurden MD, Xavier CPR, Anderhub SJ, Innocenti P, Westwood IM, Naud S, Hayes A, Box G, Valenti MR, De Haven Brandon AK, O'Fee L, Schmitt J, Woodward HL, Burke R, vanMontfort RLM, Blagg J, Raynaud FI, Eccles SA, Hoelder S, Linardopoulos S.

Br J Cancer. 2017 Apr 25;116(9):1166-1176. doi: 10.1038/bjc.2017.75. Epub 2017 Mar 23.


A fragment-based approach applied to a highly flexible target: Insights and challenges towards the inhibition of HSP70 isoforms.

Jones AM, Westwood IM, Osborne JD, Matthews TP, Cheeseman MD, Rowlands MG, Jeganathan F, Burke R, Lee D, Kadi N, Liu M, Richards M, McAndrew C, Yahya N, Dobson SE, Jones K, Workman P, Collins I, van Montfort RL.

Sci Rep. 2016 Oct 6;6:34701. doi: 10.1038/srep34701.


Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737).

Osborne JD, Matthews TP, McHardy T, Proisy N, Cheung KM, Lainchbury M, Brown N, Walton MI, Eve PD, Boxall KJ, Hayes A, Henley AT, Valenti MR, De Haven Brandon AK, Box G, Jamin Y, Robinson SP, Westwood IM, van Montfort RL, Leonard PM, Lamers MB, Reader JC, Aherne GW, Raynaud FI, Eccles SA, Garrett MD, Collins I.

J Med Chem. 2016 Jun 9;59(11):5221-37. doi: 10.1021/acs.jmedchem.5b01938. Epub 2016 May 23.


Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70.

Cheeseman MD, Westwood IM, Barbeau O, Rowlands M, Dobson S, Jones AM, Jeganathan F, Burke R, Kadi N, Workman P, Collins I, van Montfort RL, Jones K.

J Med Chem. 2016 May 26;59(10):4625-36. doi: 10.1021/acs.jmedchem.5b02001. Epub 2016 May 11.


Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach.

Innocenti P, Woodward HL, Solanki S, Naud S, Westwood IM, Cronin N, Hayes A, Roberts J, Henley AT, Baker R, Faisal A, Mak GW, Box G, Valenti M, De Haven Brandon A, O'Fee L, Saville H, Schmitt J, Matijssen B, Burke R, van Montfort RL, Raynaud FI, Eccles SA, Linardopoulos S, Blagg J, Hoelder S.

J Med Chem. 2016 Apr 28;59(8):3671-88. doi: 10.1021/acs.jmedchem.5b01811. Epub 2016 Apr 7.


8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors.

Bavetsias V, Lanigan RM, Ruda GF, Atrash B, McLaughlin MG, Tumber A, Mok NY, Le Bihan YV, Dempster S, Boxall KJ, Jeganathan F, Hatch SB, Savitsky P, Velupillai S, Krojer T, England KS, Sejberg J, Thai C, Donovan A, Pal A, Scozzafava G, Bennett JM, Kawamura A, Johansson C, Szykowska A, Gileadi C, Burgess-Brown NA, von Delft F, Oppermann U, Walters Z, Shipley J, Raynaud FI, Westaway SM, Prinjha RK, Fedorov O, Burke R, Schofield CJ, Westwood IM, Bountra C, Müller S, van Montfort RL, Brennan PE, Blagg J.

J Med Chem. 2016 Feb 25;59(4):1388-409. doi: 10.1021/acs.jmedchem.5b01635. Epub 2016 Jan 7.


Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance.

Gurden MD, Westwood IM, Faisal A, Naud S, Cheung KM, McAndrew C, Wood A, Schmitt J, Boxall K, Mak G, Workman P, Burke R, Hoelder S, Blagg J, Van Montfort RL, Linardopoulos S.

Cancer Res. 2015 Aug 15;75(16):3340-54. doi: 10.1158/0008-5472.CAN-14-3272. Epub 2015 Jul 22.


Differences between murine arylamine N-acetyltransferase type 1 and human arylamine N-acetyltransferase type 2 defined by substrate specificity and inhibitor binding.

Laurieri N, Kawamura A, Westwood IM, Varney A, Morris E, Russell AJ, Stanley LA, Sim E.

BMC Pharmacol Toxicol. 2014 Nov 29;15:68. doi: 10.1186/2050-6511-15-68.


Structure-based design of orally bioavailable 1H-pyrrolo[3,2-c]pyridine inhibitors of mitotic kinase monopolar spindle 1 (MPS1).

Naud S, Westwood IM, Faisal A, Sheldrake P, Bavetsias V, Atrash B, Cheung KM, Liu M, Hayes A, Schmitt J, Wood A, Choi V, Boxall K, Mak G, Gurden M, Valenti M, de Haven Brandon A, Henley A, Baker R, McAndrew C, Matijssen B, Burke R, Hoelder S, Eccles SA, Raynaud FI, Linardopoulos S, van Montfort RL, Blagg J.

J Med Chem. 2013 Dec 27;56(24):10045-65. doi: 10.1021/jm401395s. Epub 2013 Dec 2.


The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design.

Couty S, Westwood IM, Kalusa A, Cano C, Travers J, Boxall K, Chow CL, Burns S, Schmitt J, Pickard L, Barillari C, McAndrew PC, Clarke PA, Linardopoulos S, Griffin RJ, Aherne GW, Raynaud FI, Workman P, Jones K, van Montfort RL.

Oncotarget. 2013 Oct;4(10):1647-61.


Synthesis and evaluation of heteroaryl substituted diazaspirocycles as scaffolds to probe the ATP-binding site of protein kinases.

Allen CE, Chow CL, Caldwell JJ, Westwood IM, van Montfort RL, Collins I.

Bioorg Med Chem. 2013 Sep 15;21(18):5707-24. doi: 10.1016/j.bmc.2013.07.021. Epub 2013 Jul 19.


Fragment-based screening maps inhibitor interactions in the ATP-binding site of checkpoint kinase 2.

Silva-Santisteban MC, Westwood IM, Boxall K, Brown N, Peacock S, McAndrew C, Barrie E, Richards M, Mirza A, Oliver AW, Burke R, Hoelder S, Jones K, Aherne GW, Blagg J, Collins I, Garrett MD, van Montfort RL.

PLoS One. 2013 Jun 12;8(6):e65689. doi: 10.1371/journal.pone.0065689. Print 2013.


Scaffold-focused virtual screening: prospective application to the discovery of TTK inhibitors.

Langdon SR, Westwood IM, van Montfort RL, Brown N, Blagg J.

J Chem Inf Model. 2013 May 24;53(5):1100-12. doi: 10.1021/ci400100c. Epub 2013 May 14.


Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages.

Abuhammad A, Fullam E, Lowe ED, Staunton D, Kawamura A, Westwood IM, Bhakta S, Garner AC, Wilson DL, Seden PT, Davies SG, Russell AJ, Garman EF, Sim E.

PLoS One. 2012;7(12):e52790. doi: 10.1371/journal.pone.0052790. Epub 2012 Dec 28.


Benzimidazole inhibitors of the protein kinase CHK2: clarification of the binding mode by flexible side chain docking and protein-ligand crystallography.

Matijssen C, Silva-Santisteban MC, Westwood IM, Siddique S, Choi V, Sheldrake P, van Montfort RL, Blagg J.

Bioorg Med Chem. 2012 Nov 15;20(22):6630-9. doi: 10.1016/j.bmc.2012.09.024. Epub 2012 Sep 21.


Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.

Reader JC, Matthews TP, Klair S, Cheung KM, Scanlon J, Proisy N, Addison G, Ellard J, Piton N, Taylor S, Cherry M, Fisher M, Boxall K, Burns S, Walton MI, Westwood IM, Hayes A, Eve P, Valenti M, de Haven Brandon A, Box G, van Montfort RL, Williams DH, Aherne GW, Raynaud FI, Eccles SA, Garrett MD, Collins I.

J Med Chem. 2011 Dec 22;54(24):8328-42. doi: 10.1021/jm2007326. Epub 2011 Nov 23.


Analysis of water patterns in protein kinase binding sites.

Barillari C, Duncan AL, Westwood IM, Blagg J, van Montfort RL.

Proteins. 2011 Jul;79(7):2109-21. doi: 10.1002/prot.23032. Epub 2011 May 9.


Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars.

Westwood IM, Bhakta S, Russell AJ, Fullam E, Anderton MC, Kawamura A, Mulvaney AW, Vickers RJ, Bhowruth V, Besra GS, Lalvani A, Davies SG, Sim E.

Protein Cell. 2010 Jan;1(1):82-95. doi: 10.1007/s13238-010-0006-1. Epub 2010 Mar 18.


Novel small-molecule inhibitors of arylamine N-acetyltransferases: drug discovery by high-throughput screening.

Westwood IM, Kawamura A, Russell AJ, Sandy J, Davies SG, Sim E.

Comb Chem High Throughput Screen. 2011 Feb;14(2):117-24.


Design and evaluation of 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines as inhibitors of checkpoint and other kinases.

Matthews TP, McHardy T, Klair S, Boxall K, Fisher M, Cherry M, Allen CE, Addison GJ, Ellard J, Aherne GW, Westwood IM, van Montfort R, Garrett MD, Reader JC, Collins I.

Bioorg Med Chem Lett. 2010 Jul 15;20(14):4045-9. doi: 10.1016/j.bmcl.2010.05.096. Epub 2010 May 27.


Small molecule colorimetric probes for specific detection of human arylamine N-acetyltransferase 1, a potential breast cancer biomarker.

Laurieri N, Crawford MH, Kawamura A, Westwood IM, Robinson J, Fletcher AM, Davies SG, Sim E, Russell AJ.

J Am Chem Soc. 2010 Mar 17;132(10):3238-9. doi: 10.1021/ja909165u.


Identification of inhibitors of checkpoint kinase 1 through template screening.

Matthews TP, Klair S, Burns S, Boxall K, Cherry M, Fisher M, Westwood IM, Walton MI, McHardy T, Cheung KM, Van Montfort R, Williams D, Aherne GW, Garrett MD, Reader J, Collins I.

J Med Chem. 2009 Aug 13;52(15):4810-9. doi: 10.1021/jm900314j.


Selective small molecule inhibitors of the potential breast cancer marker, human arylamine N-acetyltransferase 1, and its murine homologue, mouse arylamine N-acetyltransferase 2.

Russell AJ, Westwood IM, Crawford MH, Robinson J, Kawamura A, Redfield C, Laurieri N, Lowe ED, Davies SG, Sim E.

Bioorg Med Chem. 2009 Jan 15;17(2):905-18. doi: 10.1016/j.bmc.2008.11.032. Epub 2008 Nov 19.


Current trends in N-acetyltransferase research arising from the 2007 International NAT Workshop.

Boukouvala S, Westwood IM, Butcher NJ, Fakis G.

Pharmacogenomics. 2008 Jun;9(6):765-71. doi: 10.2217/14622416.9.6.765.


Structure of HsaD, a steroid-degrading hydrolase, from Mycobacterium tuberculosis.

Lack N, Lowe ED, Liu J, Eltis LD, Noble ME, Sim E, Westwood IM.

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Jan 1;64(Pt 1):2-7. Epub 2007 Dec 20.


Divergence of cofactor recognition across evolution: coenzyme A binding in a prokaryotic arylamine N-acetyltransferase.

Fullam E, Westwood IM, Anderton MC, Lowe ED, Sim E, Noble ME.

J Mol Biol. 2008 Jan 4;375(1):178-91. Epub 2007 Oct 13.


Kurarinol, tyrosinase inhibitor isolated from the root of Sophora flavescens.

Ryu YB, Westwood IM, Kang NS, Kim HY, Kim JH, Moon YH, Park KH.

Phytomedicine. 2008 Aug;15(8):612-8. Epub 2007 Oct 24.


Structure and mechanism of arylamine N-acetyltransferases.

Westwood IM, Kawamura A, Fullam E, Russell AJ, Davies SG, Sim E.

Curr Top Med Chem. 2006;6(15):1641-54. Review.


Expression, purification, characterization and structure of Pseudomonas aeruginosa arylamine N-acetyltransferase.

Westwood IM, Holton SJ, Rodrigues-Lima F, Dupret JM, Bhakta S, Noble ME, Sim E.

Biochem J. 2005 Jan 15;385(Pt 2):605-12.


Synthesis and in vitro evaluation of novel small molecule inhibitors of bacterial arylamine N-acetyltransferases (NATs).

Brooke EW, Davies SG, Mulvaney AW, Okada M, Pompeo F, Sim E, Vickers RJ, Westwood IM.

Bioorg Med Chem Lett. 2003 Aug 4;13(15):2527-30.


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