Presentations and Publications

Access a wide range of resources that provide detailed information on our products, programs and collaborations.

Products

Publications

2012
+/-
- Chaneton, et al. "Serine is a natural ligand and allosteric activator of pyruvate kinase M2." Nature (2012). DOI: 10.1038/nature11540.
- Saalau-Bethell, et al. "Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function." Nature Chemical Biology (2012). DOI: 10.1038/NCHEMBIO.1081.
- Thomas G. Davies and Ian J. Tickle. "Fragment Screening Using X-Ray Crystallography." Topics in Current Chemistry 317 (2012): 33-59. DOI: 10.1007/128_2011_179.
2011
+/-
- Alessandri et al. "Induction of Eosinophil Apoptosis by the Cyclin-Dependent Kinase Inhibitor AT7519 Promotes the Resolution of Eosinophil-Dominant Allergic Inflammation." PLoS ONE 6, no. 9 (2011): e25683. DOI: 10.1371/journal.pone.0025683.
- Arkenau et al. "A phase I dose escalation study of AT9283, a small molecule inhibitor of aurora kinases, in patients with advanced solid malignancies." Annals of Oncology (2011). DOI: 10.1093/annonc/mdr451.
- Brito et al. "Comparative pre-clinical evaluation of receptor tyrosine kinase inhibitors for the treatment of multiple myeloma." Leukemia Research 35, no. 9 (2011): 1233-1240. DOI: 10.1016/j.leukres.2011.01.011.
- Heightman, Tom D. "Therapeutic prospects for epigenetic modulation." Expert Opinion on Therapeutic Targets 15, no. 6 (2011): 729-740. DOI: 10.1517/14728222.2011.561786.
- Mahadevan et al. "A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors." Annals of Oncology 22, no. 9 (2011): 2137-2143. DOI: 10.1093/annonc/mdq734.
- Paul N. Mortenson and Christopher W. Murray. "Assessing the lipophilicity of fragments and early hits." Journal of Computer-Aided Molecular Design 25, no. 7 (2011): 663-667. DOI: 10.1007/s10822-011-9435-z.
- Podesta et al. "Adaptation of the plasma inhibitory activity assay to detect Aurora, ABL and FLT3 kinase inhibition by AT9283 in pediatric leukemia." Leukemia Research 35, no. 9 (2011): 1273-1275. DOI: 10.1016/j.leukres.2011.05.022.
- Qi et al. "AT9283, a novel aurora kinase inhibitor suppresses tumor growth in aggressive B-cell lymphomas." International Journal of Cancer (2011). DOI: 10.1002/ijc.26324.
- Santo et al. "Antimyeloma Activity of a Multitargeted Kinase Inhibitor, AT9283, via Potent Aurora Kinase and STAT3 Inhibition Either Alone or in Combination with Lenalidomide." Clinical Cancer Research 17, no. 10 (2011): 3259–71. DOI: 10.1158/1078-0432.CCR-10-3012.
- Squires et al. "Potent, selective inhibitors of Fibroblast Growth Factor Receptor define Fibroblast Growth Factor dependence in pre-clinical cancer models." Molecular Cancer Therapeutics 10, no. 22 (2011): 1542-1552. DOI: 10.1158/1535-7163.MCT-11-0426.
- Verdonk et al. "Docking performance of fragments and drug-like compounds." Journal of Medicinal Chemistry 54, no. 15 (2011): 5422–5431. DOI: 10.1021/jm200558u.
- Williams, Glyn. "The pyramid approach to fragment-based biophysical screening." In Label-Free Technologies for Drug Discovery, edited by Matthew Cooper and Lorenz M. Mayr, 241-253. Chichester, UK: John Wiley & Sons Ltd (2011). ISBN: 978-0-470-74683-7.
- Yap et al. "Preclinical Pharmacology, Antitumor Activity, and Development of Pharmacodynamic Markers for the Novel, Potent AKT Inhibitor CCT128930." Molecular Cancer Therapeutics 10, no. 2 (2011): 360-71. DOI: 10.1158/1535-7163.MCT-10-0760.
2010
+/-
- Cho et al. "4-(Pyrazol-4-yl)-pyrimidines as Selective Inhibitors of Cyclin-Dependent Kinase 4/6." Journal of Medicinal Chemistry 53, no. 22 (2010): 7938–7957. DOI: 10.1021/jm100571n.
- Christopher W. Murray and Tom L. Blundell. "Structural Biology in Fragment-Based Drug Design." Current Opinion in Structural Biology 20, no. 4 (2010): 497-507. DOI: 10.1016/j.sbi.2010.04.003.
- Dawson M. A. et al. "AT9283, a potent inhibitor of the Aurora kinases and Jak2, has therapeutic potential in myeloproliferative disorders." British Journal of Haematology 150, no. 1 (2010): 46-57. DOI: 10.1111/j.1365-2141.2010.08175.x.
- McHardy et al. "Discovery of 4-Amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides As Selective, Orally Active Inhibitors of Protein Kinase B (Akt)." Journal of Medicinal Chemistry 53, no. 5 (2010): 2239–2249. DOI: 10.1021/jm901788j.
- Murray et al. "Fragment-Based Drug Discovery Applied to HSP90. Discovery of Two Lead Series with High Ligand Efficiency." Journal of Medicinal Chemistry 53, no. 16 (2010): 5942–5955. DOI: 10.1021/jm100059d.
- Santo et al. "AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition." Oncogene 29, no. 16 (2010): 2325-2336. DOI: 10.1038/onc.2009.510.
- Squires M. et al. "AT7519, a Cyclin-Dependent Kinase Inhibitor, Exerts Its Effects by Transcriptional Inhibition in Leukemia Cell Lines and Patient Samples." Molecular Cancer Therapeutics 9, no. 4 (2010): 920-928. DOI: 10.1158/1535-7163.MCT-09-1071.
- Tanaka et al. "Activity of the multi-targeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL positive leukemic cells." Blood 116, no. 12 (2010): 2089-2095. DOI: 10.1182/blood-2009-03-211466.
- Woodhead et al. "Discovery of (2,4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a Novel Inhibitor of the Molecular Chaperone Hsp90 by Fragment Based Drug Design." Journal of Medicinal Chemistry 53, no. 16 (2010): 5956–5969. DOI: 10.1021/jm100060b.
2009
+/-
- Christopher W. Murray and David C. Rees. "The rise of fragment based drug discovery." Nature Chemistry 1, no. 3 (2009): 187-192. DOI: 10.1038/nchem.217.
- Curry J. et al. "Aurora kinase inhibition in mitosis: Strategies for optimising the use of aurora kinase inhibitors such as AT9283." Cell Cycle 8, no. 12 (2009): 1-9. DOI: 10.4161/cc.8.12.8741.
- Davies et al. "Fragment-Based Discovery of Inhibitors of Protein Kinase B." Current Topics in Medicinal Chemistry 9, no. 18 (2009): 1705-1717.
- Day et al. "Crystal structure of human CDK4 in complex with a D-type cyclin." Proceedings of the National Academy of Sciences 106, no. 11 (2009): 4166-4170. DOI: 10.1073/pnas.0809645106.
- Howard et al. "Fragment-Based Discovery of the Pyrazol-4-yl urea (AT9283), a Multi-targeted Kinase Inhibitor with Potent Aurora Kinase Activity." Journal of Medicinal Chemistry 52, no. 2 (2009): 379–388. DOI: 10.1021/jm800984v.
2008
+/-
- Frederickson et al. "Fragment-Based Discovery of Mexiletine Derivatives as Orally Bioavailable Inhibitors of Urokinase-Type Plasminogen Activator." Journal of Medicinal Chemistry 51, no. 2 (2008): 183–186. DOI: 10.1021/jm701359z.
- Marcel L. Verdonk and David C. Rees. "Group Efficiency: A Guideline for Hits-to-Leads Chemistry." ChemMedChem 3, no. 8 (2008): 1179–1180. DOI: 10.1002/cmdc.200800132.
- Miles Congreve et al. "Recent Developments in Fragment-Based Drug Discovery." Journal of Medicinal Chemistry 51, no. 13 (2008): 3661–3680. DOI: 10.1021/jm8000373.
- Paul G. Wyatt, Andrew J. Woodhead, Valerio Berdini et al. "Identification of N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a Novel Cyclin Dependent Kinase Inhibitor Using Fragment-Based X-Ray Crystallography and Structure Based Drug Design." Journal of Medicinal Chemistry 51, no. 16 (2008): 4986–4999. DOI: 10.1021/jm800382h.
- Verdonk et al. "Protein−Ligand Docking against Non-Native Protein Conformers." Journal of Chemical Information and Modeling 48, no. 11 (2008): 2214–2225. DOI: 10.1021/ci8002254.
2007
+/-
- Christopher W. Murray et al. "Application of Fragment Screening by X-ray Crystallography to β-Secretase." Journal of Medicinal Chemistry 50, no. 6 (2007): 1116–1123. DOI: 10.1021/jm0611962.
- Jhoti, Harren; Leach, Andrew (Eds.). "Structure-based Drug Discovery." Springer, XII, 252p., Hardcover (2007). ISBN: 978-1-4020-4406-9.
- Michael J. Hartshorn, et al. "Diverse, High-Quality Test Set for the Validation of Protein−Ligand Docking Performance." Journal of Medicinal Chemistry 50, no. 4 (2007): 726–741. DOI: 10.1021/jm061277y.
- Miles Congreve et al. "Application of Fragment Screening by X-ray Crystallography to the Discovery of Aminopyridines as Inhibitors of β-Secretase." Journal of Medicinal Chemistry 50, no. 6 (2007): 1124–1132. DOI: 10.1021/jm061197u.
- P. Day, et al. "Structure of a CBS-domain pair from the regulatory γ1 subunit of human AMPK in complex with AMP and ZMP." Acta Crystallographica D63 (2007): 587-596. DOI: 10.1107/S0907444907009110.
- Saxty et al. "Identification of Inhibitors of Protein Kinase B Using Fragment-Based Lead Discovery." Journal of Medicinal Chemistry 50, no. 10 (2007): 2293–2296. DOI: 10.1021/jm070091b.
2006
+/-
- Davies Thomas G., et al. "Pyramid: An integrated platform for fragment-based drug discovery." Fragment-based approaches in drug discovery: Volume 34, Chapter 10, pp 193-214. Edited by W Jahnke and D. A. Erlanson. WILEY-VCG Verlag GmbH & Co. KGaA, Weinheim (2007). ISBN: 978-3-527-31291-7.
- Howard, N., et al. "Application of Fragment Screening and Fragment Linking to the Discovery of Novel Thrombin Inhibitors." Journal of Medicinal Chemistry 49, no. 4 (2006): 1346–1355. DOI: 10.1021/jm050850v.
- Mooij W. T. M. et al. "Automated Protein–Ligand Crystallography for Structure-Based Drug Design." ChemMedChem 1, no. 8 (2006): 827–838. DOI: 10.1002/cmdc.200600074.
- Murray C. W., Verdonk et al. "Entropic consequences of linking ligands." Fragment-based approaches in drug discovery: Volume 34, Chapter 3, pp 55-66. Edited by W Jahnke and D. A. Erlanson. WILEY-VCG Verlag GmbH & Co. KGaA, Weinheim (2006). ISBN: 978-3-527-31291-7.
2005
+/-
- Gill, A., et al. "The Discovery of Novel Protein Kinase Inhibitors by Using Fragment-Based High-Throughput X-ray Crystallography." ChemBioChem 6, no. 3 (2005): 506–512. DOI: 10.1002/cbic.200400188.
- Gill, A.L., et al. "Identification of Novel p38α MAP Kinase Inhibitors Using Fragment-Based Lead Generation." Journal of Medicinal Chemistry 48, no. 2 (2005): 414–426. DOI: 10.1021/jm049575n.
- Hartshorn, M.J., et al. "Fragment-Based Lead Discovery Using X-ray Crystallography." Journal of Medicinal Chemistry 48, no. 2 (2005): 403–413. DOI: 10.1021/jm0495778.
- Kirton, S.B., et al. "Prediction of binding modes for ligands in the cytochromes P450 and other heme-containing proteins." Proteins: Structure, Function, and Bioinformatics 58, no. 4 (2005): 836–844. DOI: 10.1002/prot.20389.
- Miles Congreve, Christopher W. Murray and Tom L. Blundell. "Keynote review: Structural biology and drug discovery." Drug Discovery Today 10, no. 13 (2005): 895–907. DOI: 10.1016/S1359-6446(05)03484-7.
- Robin A.E. Carr, Miles Congreve, Christopher W. Murray, David C. Rees. "Fragment-based lead discovery: leads by design." Drug Discovery Today 10, no. 14 (2005): 987–992. DOI: 10.1016/S1359-6446(05)03511-7.
- Thompson N., Lyons J. "Recent progress in targeting the Raf/MEK/ERK pathway with inhibitors in cancer drug discovery." Current Opinion in Pharmacology 5, no. 4 (2005): 350–356. DOI: 10.1016/j.coph.2005.04.007.
2004
+/-
- Gill, A. L. "New Lead Generation Strategies for Protein Kinase Inhibitors - Fragment Based Screening Approaches." Mini-Reviews in Medicinal Chemistry 4, no. 3 (2004): 301-311.
- Patel, S., et al. "Apo and Inhibitor Complex Structures of BACE (β-secretase)." Journal of Molecular Biology 343, no. 2 (2004): 407–416. DOI: 10.1016/j.jmb.2004.08.018.
- Rees, D.C., et al. "Fragment-based lead discovery." Nature Reviews Drug Discovery 3 (2004): 660-672. DOI: 10.1038/nrd1467.
- Tickle, I., et al. "High-throughput protein crystallography and drug discovery." Chemical Society Reviews 33, no. 8 (2004): 558-565. DOI: 10.1039/B314510G.
- Verdonk M. L., Hartshorn, M. J. "Structure-guided fragment screening for lead discovery." Current Opinion in Drug Discovery and Development 7 (2004): 404-410.
- Verdonk, M. L., et al. "Virtual Screening Using Protein−Ligand Docking: Avoiding Artificial Enrichment." Journal of Chemical Information and Modeling 44, no. 3 (2004): 793–806. DOI: 10.1021/ci034289q.
- Williams, P. A., et al. "Crystal Structures of Human Cytochrome P450 3A4 Bound to Metyrapone and Progesterone." Science 305, no. 5684 (2004): 683-686. DOI: 10.1126/science.1099736.
2003
+/-
- Birch, L., et al. "Sensitivity of molecular docking to induced fit effects in influenza virus neuraminidase." Journal of Computer-Aided Molecular Design 16, no. 12 (2003): 855-869. DOI: 10.1023/A:1023844626572.
- Congreve, M.S. et al. "Detection of Ligands from a Dynamic Combinatorial Library by X-ray Crystallography." Angewandte Chemie International Edition 42, no. 37 (2003): 4479–4482. DOI: 10.1002/anie.200351951.
- Congreve, M.S. et al. "A ‘Rule of Three’ for fragment-based lead discovery?." Drug Discovery Today 8, no. 19 (2003): 876–877. DOI: 10.1016/S1359-6446(03)02831-9.
- Frederickson M., Vuillard, L. et al. "Novel selenium containing non-detergent sulphobetaines." Tetrahedron Letters 44, no. 43 (2003): 7925–7928. DOI: 10.1016/j.tetlet.2003.09.004.
- Hartshorn, MJ. "AstexViewer™: a visualisation aid for structure-based drug design." Journal of Computer-Aided Molecular Design 16, no. 12 (2003): 871-881. DOI: 10.1023/A:1023813504011.
- Sharff A. , Jhoti, H. "High-throughput crystallography to enhance drug discovery." Current Opinion in Chemical Biology 7, no. 3 (2003): 340–345. DOI: 10.1016/S1367-5931(03)00062-0.
- van Montfort, R.L.M., et al. "Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B." Nature 423 (2003): 773-777. DOI: 10.1038/nature01681.
- Verdonk, M. L., et al. "Improved protein–ligand docking using GOLD." Proteins: Structure, Function, and Bioinformatics 52, no. 4 (2003): 609–623. DOI: 10.1002/prot.10465.
- Watson P. Verdonk, M. , Hartshorn M.J. "A web-based platform for virtual screening." Journal of Molecular Graphics and Modelling 22, no. 1 (2003): 71–82. DOI: 10.1016/S1093-3263(03)00137-2.
- Williams, P.A., et al. "Crystal structure of human cytochrome P450 2C9 with bound warfarin." Nature 424, no. 6947 (2003): 464-468. DOI: 10.1038/nature01862.
- Yon J., Jhoti, H. "High-throughput structural genomics and proteomics: where are we now?." Targets 2, no. 5 (2003): 201–207. DOI: 10.1016/S1477-3627(03)02348-1.
2002
+/-
- Blundell T.L., Jhoti, H. et al. "High-throughput crystallography for lead discovery in drug design." Nature Reviews Drug Discovery 1 (2002): 45-54. DOI: 10.1038/nrd706.
- Carr R., Hann, M. "The right road to drug discovery?." Modern Drug Discovery 5, no. 4 (2002): 45-48.
- Carr R., Jhoti, H. "Structure-based screening of low-affinity compounds." Drug Discovery Today 7, no. 9 (2002): 522–527. DOI: 10.1016/S1359-6446(02)02245-6.
- Murray C.W., Verdonk, M.L. "The consequences of translational and rotational entropy lost by small molecules on binding to proteins." Journal of Computer-Aided Molecular Design 16, no. 10 (2002): 741-753. DOI: 10.1023/A:1022446720849.
2001
+/-
- Jhoti H. "Structural genomics: lessons to be learnt." Drug Discovery Today 6, no. 24 (2001): 1261–1262. DOI: 10.1016/S1359-6446(01)02114-6.
- Jhoti, H. "High-throughput structural proteomics using x-rays." Trends in Biotechnology 19, no. 10 (2001): S67–S71. DOI: 10.1016/S0167-7799(01)01791-7.

Discovery

Partnered Programs

+/-
- 2011 EORTC_Mouse PK of AKT Inhibitor CCT128930 from Caudal Dried Blood Spots
- 2009 EORTC_CCT129254 (AT11854) is a Well Tolerated, Orally BioAvail. Inhibitor of AKT/PKB
+/-

No public presentations available at this time.
+/-

No public presentations available at this time.
+/-
+/-

No public presentations available at this time.

Presentations and Publications

Products

AT13387 – HSP90 inhibitor (GIST, Prostate & Lung)
+/-

SGI110 – DNMT inhibitor (MDS, AML, Ovarian & Liver)
+/-

Amuvatinib/MP470 (SCLC)
+/-

AT7519 – CDK inhibitor (MM)
+/-

AT9283 – JAK/Aurora inhibitor (MM)
+/-

AT13148 – AGC kinase inhibitor
+/-

LEE011 – CDK4 inhibitor (Oncology)
+/-

AZD5363 – PKB/Akt inhibitor (Oncology)
+/-

JNJ42756493 - FGFr inhibitor (Oncology)
+/-

AZD3293 – BACE inhibitor (Alzheimer’s)
+/-

Publications

2012
+/-

2011
+/-

2010
+/-

2009
+/-

2008
+/-

2007
+/-

2006
+/-

2005
+/-

2004
+/-

2003
+/-

2002
+/-

2001
+/-

Discovery

Epigenetics
+/-

HCV NS3
+/-

Inhibitor of Apoptosis Protein (IAP)
+/-

Technology
+/-

Partnered Programs

+/-

+/-

+/-

+/-

+/-

Presentations and Publications

Products

AT13387 – HSP90 inhibitor (GIST, Prostate & Lung)+/-

SGI110 – DNMT inhibitor (MDS, AML, Ovarian & Liver)+/-

Amuvatinib/MP470 (SCLC)+/-

AT7519 – CDK inhibitor (MM)+/-

AT9283 – JAK/Aurora inhibitor (MM)+/-

AT13148 – AGC kinase inhibitor+/-

LEE011 – CDK4 inhibitor (Oncology)+/-

AZD5363 – PKB/Akt inhibitor (Oncology)+/-

JNJ42756493 - FGFr inhibitor (Oncology)+/-

AZD3293 – BACE inhibitor (Alzheimer’s)+/-

Publications

2012+/-

2011+/-

2010+/-

2009+/-

2008+/-

2007+/-

2006+/-

2005+/-

2004+/-

2003+/-

2002+/-

2001+/-

Discovery

Epigenetics+/-

HCV NS3+/-

Inhibitor of Apoptosis Protein (IAP)+/-

Technology+/-

Partnered Programs

+/-

+/-

+/-

+/-

+/-

AT13387 – HSP90 inhibitor (GIST, Prostate & Lung)
+/-

SGI110 – DNMT inhibitor (MDS, AML, Ovarian & Liver)
+/-

Amuvatinib/MP470 (SCLC)
+/-

AT7519 – CDK inhibitor (MM)
+/-

AT9283 – JAK/Aurora inhibitor (MM)
+/-

AT13148 – AGC kinase inhibitor
+/-

LEE011 – CDK4 inhibitor (Oncology)
+/-

AZD5363 – PKB/Akt inhibitor (Oncology)
+/-

JNJ42756493 - FGFr inhibitor (Oncology)
+/-

AZD3293 – BACE inhibitor (Alzheimer’s)
+/-

2012
+/-

2011
+/-

2010
+/-

2009
+/-

2008
+/-

2007
+/-

2006
+/-

2005
+/-

2004
+/-

2003
+/-

2002
+/-

2001
+/-

Epigenetics
+/-

HCV NS3
+/-

Inhibitor of Apoptosis Protein (IAP)
+/-

Technology
+/-