Staff Profile

Current position

Professor of Cancer Structural Biology

Area of expertise

Cell cycle structural biology       

Phosphorylation transcription

Since October 2011, I have been Professor of Cancer Structural Biology at Newcastle University and a member of the Cancer Research UK Newcastle Drug Discovery Group. My group is pursuing structure-function studies of protein complexes involved in regulating transcription and progression through the eukaryotic cell cycle. We are also providing structural biology support to projects within the CRUK Newcastle DDG. I recently joined the Translational and Clinical Research Institute within the Faculty of Medical Sciences.

I studied Biochemistry at Corpus Christi College, the University of Oxford and then moved to the laboratory of Victor Ling at the Ontario Cancer Institute, Toronto to complete my PhD. I returned to Oxford in 1991 as a Junior Research Fellow of the National Cancer Institute of Canada to join the laboratories of Professor Paul Nurse and Professor Louise Johnson to pursue structural studies of cyclin-dependent protein kinases (CDKs) and their regulators. I was awarded a Royal Society University Research Fellowship in 1995 and appointed to a University Lecturership in the Laboratory of Molecular Biophysics, University of Oxford in 1998. During my time at Oxford I held a College Fellowship at St. Cross College, where I am now an Emeritus Fellow and a Lecturership at Trinity College. 

External research roles and memberships

2018-present CRUK Science Committee/ Discovery Research Committee, Vice Chair (2023-present)

2016-2023 MRC Non-Clinical Training and Career Development Panel, Deputy Chair (2019-2023)

2012-present Fellow, Royal Society of Biology

2003-present Faculty of 1000

Honours and awards

2014   MRC Suffrage Science Award

Google scholar: Click here.

Research interests

Structural and functional characterisation of the cyclin-dependent protein kinase (CDK) family

Development of small molecule CDK inhibitors

Biophysical assays and structure determination for anti-cancer drug design

Current work

The growth and division of cells is strictly controlled at the molecular level by a number of enzymes that include the cyclin dependent protein kinases (CDKs). CDKs 1, 2, 4 and 6 are switched on and off in an orderly sequence, to ensure that cell division starts and stops at the required time. Other members of the CDK family (for example CDKs 7, 8 and 9) are also important for the control of transcription, the process by which genes are transcribed into messenger RNA that in turn serves as the template for protein synthesis. Regulation of transcription ensures the timely expression of proteins required for cell growth and differentiation. Errors in either the control of cell cycle progression or transcription can lead to uncontrolled cell growth and proliferation.

Although CDK family members are closely related in sequence, biological studies have revealed that each has unique properties. Our work, primarily using the technique of X-ray crystallography, allows us to see the structures of CDKs and the complexes they form at atomic resolution and to learn how they differ from each other. To this end we characterise and reconstitute selected CDK-containing complexes using heterologous expression systems and then study them by structural, biochemical, biophysical and cell-based methods. Aberrant CDK activity has been linked to cancer, neurological diseases, and rheumatoid arthritis. CDK-selective inhibitors in clinical trials for the treatment of cancer act by binding to the CDK active site to block CDK activity. Compounds that block other interactions made by CDK-cyclin complexes represent an alternative target for CDK-directed therapies. Our work aims to identify CDK-cyclin protein interaction sites to further understand the regulation of this important enzyme class and to aid the further development of CDK inhibitors. 

For further details about our work, please visit our web pages:

https://research.ncl.ac.uk/cellcyclestructuralbiology/

https://research.ncl.ac.uk/drugdiscovery/

Selected Publications

Salamina, M., Montefiore, B.C., Liu, M., Wood, D.J., Heath, R., Ault, J.R., Wang, L.-Z., Korolchuk, S., Baslé, A., Pastok, M.W., Reeks, J., Tatum, N.J., Sobott, F., Arold, S.T., Pagano, M., Noble, M.E.M., Endicott, J.A. (2021) Discriminative SKP2 Interactions with CDK-cyclin complexes support a cyclin A-specific role in p27KIP1 degradation. J. Mol. Biol. 433:166795.

Wood, D.J., Korolchuk, S. Tatum N.J., Wang, L.-Z. Endicott, J.A. Noble, M.E.M., Martin, M.P. (2019) Differences in the conformational energy landscape of CDK1 and CDK2 suggest a mechanism for achieving selective CDK inhibition. Cell Chem. Biol. 26:121-130.

Wood DJ, Endicott JA. (2018) Structural insights into the functional diversity of the CDK-cyclin family. Open Biol. 8(9). pii: 180112. doi: 10.1098/rsob.180112. 

Hallett, S.T., Pastok, M.W., Morgan, R.M.L., Wittner, A., Blundell, K.L.I.M., Felletar, I., Wedge, S.R., Prodromou, C., Noble, M.E.M., Pearl, L.H. and Endicott, J.A. (2017) Differential regulation of G1 CDK complexes by the Hsp90-Cdc37 chaperone system. Cell Repts, 21, 1-13.

Brown, N.R., Korolchuk, S., Martin, M., Moukhametzianov, R., Stanley, W. Noble, M.E.M. and Endicott, J.A. (2015) CDK1 structures reveal conserved and unique features of the essential cell cycle CDK. Nature Comms, 6: 6769.

Takaki, T., Echalier, A., Brown, N.R., Hunt, T., Endicott, J.A., and Noble, M.E.M., (2009) The structure of CDK4/cyclin D3 has implications for models of CDK activation. Proc Nat Acad Sci USA 106, 4171-4176. 

Theme web pages

Discovery of Medicines

Teaching and supervision

PhD and MRes student supervision

I look forward to welcoming Masters and undergraduate project students with an interest in

            Cell cycle regulation

            CDK structural biology

Undergraduate course BGM2002, Biochemistry and Genetics of Signalling and the Cell Cycle

Undergraduate course BGM2060, Proteins and Enzymes

MRes course MMB8008, Chromosome Biology and Cell Cycle Control in Health and Disease

• Articles

  • al-Rawi A, Kaye E, Korolchuk S, Endicott JA, Ly T. Cyclin A and Cks1 promote kinase consensus switching to non-proline-directed CDK1 phosphorylation. Cell Reports 2023, 42(3), 112139.
  • Miller DC, Reuillon T, Molyneux L, Blackburn T, Cook SJ, Edwards N, Endicott JA, Golding BT, Griffin RJ, Hardcastle I, Harnor SJ, Heptinstall A, Lochhead P, Martin MP, Martin NC, Myers S, Newell DR, Noble RA, Phillips N, Rigoreau L, Thomas H, Tucker JA, Wang L-Z, Waring MJ, Wong A-C, Wedge SR, Noble MEM, Cano C. Parallel Optimization of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Kinase Domain Inhibitor. Journal of Medicinal Chemistry 2022, 65(9), 6513-6540.
  • Davison G, Martin MP, Turberville S, Dormen S, Heath R, Heptinstall AB, Lawson M, Miller DC, Ng YM, Sanderson JN, Hope I, Wood DJ, Cano C, Endicott JA, Hardcastle IR, Noble MEM, Waring MJ. Mapping ligand interactions of bromodomains BRD4 and ATAD2 with FragLites and PepLites ─ Halogenated probes of druglike and peptide-like molecular interactions. Journal of Medicinal Chemistry 2022, 65(22), 15416-15432.
  • Salamina M, Montefiore BC, Liu M, Wood DJ, Heath R, Ault JR, Wang L-Z, Korolchuk S, Basle A, Pastok MW, Reeks J, Tatum NJ, Sobott F, Arold ST, Pagano M, Noble MEM, Endicott JA. Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation. Journal of Molecular Biology 2021, 433(5), 166795.
  • Al-Khawaldeh I, Aldred GG, Alyassiri M, Basmadjian C, Bordoni C, Harnor SJ, Heptinstall AB, Hobson SJ, Jennings CE, Khalifa S, Lebraud H, Miller DC, Shrives HJ, de Souza JV, Stewart HL, Temple M, Totobenazara J, Tucker JA, Tudhope SJ, Wang LZ, Bronowska AK, Cano C, Endicott JA, Golding BT, Hardcastle IR, Hickson I, Wedge SR, Willmore E, Noble MEM, Waring MJ. An alkynylpyrimidine-based covalent inhibitor that targets a unique cysteine in NF-κB-inducing kinase (NIK). Journal of Medicinal Chemistry 2021, 64(14), 10001-10018.
  • 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 L-Z, Wong A-C, Noble MEM, Wedge SR, Cano C. Identification of a novel orally bioavailable ERK5 inhibitor with selectivity over p38α and BRD4. European Journal of Medicinal Chemistry 2019, 178, 530-543.
  • Wood D, Lopez-Fernandez JD, Knight LE, Al-Khawaldeh I, Gai C, Lin S, Martin MP, Miller DC, Cano C, Endicott JA, Hardcastle IR, Noble MEM, Waring MJ. FragLites - minimal, halogenated fragments displaying pharmacophore doublets. An efficient approach to druggability assessment and hit generation. Journal of Medicinal Chemistry 2019, 62(7), 3741-3752.
  • Wood DJ, Korolchuk S, Tatum NJ, Wang L-Z, Endicott JA, Noble MEM, Martin MP. Differences in the conformational energy landscape of CDK1 and CDK2 suggest a mechanism for achieving selective CDK inhibition. Cell Chemical Biology 2019, 26(1), 121-130.e5.
  • 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. Identification of a novel ligand for the ATAD2 bromodomain with selectivity over BRD4 through a fragment growing approach. Organic and Biomolecular Chemistry 2018, 16(11), 1843-1850.
  • Martin MP, Endicott JA, Noble MEM. Structure-based discovery of cyclin-dependent protein kinase inhibitors. Essays in Biochemistry 2017, 61(5), 439-452.
  • Hallett ST, Pastok MW, Morgan RML, Wittner A, Blundell KLIM, Felletar I, Wedge SR, Prodromou C, Noble MEM, Pearl LH, Endicott JA. Differential Regulation of G1 CDK Complexes by the Hsp90-Cdc37 Chaperone System. Cell Reports 2017, 21(5), 1386-1398.
  • Coxon C, Anscombe E, Harnor S, Martin M, Carbain B, Golding B, Hardcastle I, Harlow L, Korolchuk S, Matheson C, Newell D, Noble M, Sivaprakasam M, Tudhope SJ, Turner D, Wang L, Wedge SR, Wong C, Griffin R, Endicott J, Cano C. Cyclin-Dependent Kinase (CDK) Inhibitors; Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines. Journal of Medicinal Chemistry 2017, 60, 1746-1767.
  • 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 MEM, Wedge SR, Endicott JA, Griffin RJ. Identification and characterization of an irreversible inhibitor of CDK2. Chemistry & Biology 2015, 22(9), 1159-1164.
  • Brown NR, Korolchuk S, Martin MP, Stanley WA, Moukhametzianov R, Noble MEM, Endicott JA. CDK1 structures reveal conserved and unique features of the essential cell cycle CDK. Nature Communications 2015, 6, 6769.
  • Echalier A, Hole AJ, Lolli G, Endicott JA, Noble MEM. An Inhibitor's-Eye View of the ATP-Binding Site of CDKs in Different Regulatory States. ACS Chemical Biology 2014, 9(6), 1251-1256.
  • Lu M, Zak J, Chen SO, Sanchez-Pulido L, Severson DT, Endicott J, Ponting CP, Schofield CJ, Lu X. A Code for RanGDP Binding in Ankyrin Repeats Defines a Nuclear Import Pathway. Cell 2014, 157(5), 1130-1145.
  • Carbain B, Paterson DJ, Anscombe E, Campbell AJ, Cano C, Echalier A, Endicott JA, Golding BT, Haggerty K, Hardcastle IR, Jewsbury PJ, Newell DR, Noble MEM, Roche C, Wang LZ, Griffin RJ. 8-Substituted O-6-Cyclohexylmethylguanine CDK2 Inhibitors: Using Structure-Based Inhibitor Design to Optimize an Alternative Binding Mode. Journal of Medicinal Chemistry 2014, 57(1), 56-70.
  • Anil B, Riedinger C, Endicott JA, Noble MEM. The structure of an MDM2-Nutlin-3a complex solved by the use of a validated MDM2 surface-entropy reduction mutant. Acta Crystallographica Section D: Biological Crystallography 2013, 69(8), 1358-1366.
  • Shao H, Shi SH, Huang SL, Hole AJ, Abbas AY, Baumli S, Liu XR, Lam F, Foley DW, Fischer PM, Noble M, Endicott JA, Pepper C, Wang SD. Substituted 4-(Thiazol-5-yl)-2-(phenylamino)pyrimidines Are Highly Active CDK9 Inhibitors: Synthesis, X-ray Crystal Structures, Structure-Activity Relationship, and Anticancer Activities. Journal of Medicinal Chemistry 2013, 56(3), 640-659.
  • Endicott JA, Noble MEM. Structural characterization of the cyclin-dependent protein kinase family. Biochemical Society Transactions 2013, 41(4), 1008-1016.
  • Hole AJ, Baumli S, Shao H, Shi SH, Huang SL, Pepper C, Fischer PM, Wang SD, Endicott JA, Noble ME. Comparative Structural and Functional Studies of 4-(Thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile CDK9 Inhibitors Suggest the Basis for Isotype Selectivity. Journal of Medicinal Chemistry 2013, 56(3), 660-670.
  • Medina B, Paraskevopoulos K, Boehringer J, Sznajder A, Robertson M, Endicott J, Gordon C. The ubiquitin-associated (UBA) 1 domain of Schizosaccharomyces pombe Rhp23 is essential for the recognition of ubiquitin-proteasome system substrates both in Vitro and in Vivo. Journal of Biological Chemistry 2012, 287(50), 42344-42351.
  • Baumli S, Hole AJ, Wang LZ, Noble MEM, Endicott JA. The CDK9 Tail Determines the Reaction Pathway of Positive Transcription Elongation Factor b. Structure 2012, 20(10), 1788-1795.
  • Baumli S, Hole AJ, Noble MEM, Endicott JA. The CDK9 C-helix Exhibits Conformational Plasticity That May Explain the Selectivity of CAN508. ACS chemical biology 2012, 7(5), 811-816.
  • Boehringer J, Riedinger C, Paraskevopoulos K, Johnson EOD, Lowe ED, Khoudian C, Smith D, Noble MEM, Gordon C, Endicott JA. Structural and functional characterization of Rpn12 identifies residues required for Rpn10 proteasome incorporation. Biochemical Journal 2012, 448(1), 55-65.
  • Riedinger C, Noble ME, Wright DJ, Mulks F, Hardcastle I, Endicott JA, McDonnell JM. Understanding small-molecule binding to MDM2: Insights into structural effects of isoindolinone inhibitors from NMR spectroscopy. Chemical Biology and Drug Design 2011, 77(5), 301-308.
  • Watson AF, Liu JF, Bennaceur K, Drummond CJ, Endicott JA, Golding BT, Griffin RJ, Haggerty K, Lu XH, McDonnell JM, Newell DR, Noble MEM, Revill CH, Riedinger C, Xu Q, Zhao Y, Lunec J, Hardcastle IR. MDM2-p53 protein-protein interaction inhibitors: A-ring substituted isoindolinones. Bioorganic & Medicinal Chemistry Letters 2011, 21(19), 5916-5919.
  • Hardcastle IR, Liu J, Valeur E, Watson A, Ahmed SU, Blackburn TJ, Bennaceur K, Clegg W, Drummond C, Endicott JA, Golding BT, Griffin RJ, Gruber J, Haggerty K, Harrington RW, Hutton C, Kemp S, Lu X, McDonnell JM, Newell DR, Noble ME, Payne SL, Revill CH, Riedinger C, Xu Q, Lunec J. Isoindolinone Inhibitors of the Murine Double Minute 2 (MDM2)-p53 Protein-Protein Interaction: Structure-Activity Studies Leading to Improved Potency. Journal of Medicinal Chemistry 2011, 54(5), 1233-1243.
  • Riedinger C, Boehringer J, Trempe JF, Lowe ED, Brown NR, Gehring K, Noble MEM, Gordon C, Endicott JA. Structure of Rpn10 and Its Interactions with Polyubiquitin Chains and the Proteasome Subunit Rpn12. Journal of Biological Chemistry 2010, 285(44), 33992-34003.
  • Baumli S, Endicott JA, Johnson LN. Halogen Bonds Form the Basis for Selective P-TEFb Inhibition by DRB. Chemistry & Biology 2010, 17(9), 931-936.
  • Bettayeb K, Baunbæk D, Delehouze C, Loaëc N, Hole AJ, Baumli S, Endicott JA, Douc-Rasy S, Bénard J, Oumata N, Galons H, Meijer L. CDK Inhibitors Roscovitine and CR8 Trigger Mcl-1 Down-Regulation and Apoptotic Cell Death in Neuroblastoma Cells. Genes & Cancer 2010, 1(4), 369-380.
  • Trempe JF, Brown NR, Noble MEM, Endicott JA. A new crystal form of Lys48-linked diubiquitin. Acta Crystallographica. Section F: Structural Biology and Crystallization Communications 2010, 66(9), 994-998.
  • Takaki T, Echalier A, Brown NR, Hunt T, Endicott JA, Noble MEM. The structure of CDK4/cyclin D3 has implications for models of CDK activation. Proceedings of the National Academy of Sciences 2009, 106(11), 4171-4176.
  • Merckx A, Echalier A, Langford K, Sicard A, Langsley G, Joore J, Doerig C, Noble M, Endicott J. Structures of P. falciparum protein kinase 7 identify an activation motif and leads for inhibitor design. Structure 2008, 16(2), 228-238.
  • Echalier A, Bettayeb K, Ferandin Y, Lozach O, Clement M, Valette A, Liger F, Marquet B, Morris JC, Endicott JA, Joseph B, Meijer L. Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): Synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin complex. Journal of Medicinal Chemistry 2008, 51(4), 737-751.
  • Bettayeb K, Oumata N, Echalier A, Ferandin Y, Endicott JA, Galons H, Meijer L. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. Oncogene 2008, 27(44), 5797-5807.
  • Riedinger C, Endicott JA, Kemp SJ, Smyth LA, Watson A, Valeur E, Golding BT, Griffin RJ, Hardcastle IR, Noble ME, McDonnell JM. Analysis of Chemical Shift Changes Reveals the Binding Modes of Isoindolinone Inhibitors of the MDM2-p53 Interaction. Journal of the American Chemical Society 2008, 130(47), 16038-16044.
  • Marchetti F, Sayle KL, Bentley J, Clegg W, Curtin NJ, Endicott JA, Golding BT, Griffin RJ, Haggerty K, Harrington RW, Mesguiche V, Newell DR, Noble MEM, Parsons RJ, Pratt DJ, Wang L, Hardcastle IR, Mesguiche V, Newell DR, Noble MEM, Parsons RJ, Pratt DJ, Wang L, Hardcastle IR. Structure-based design of 2-arylamino-4-cyclohexylmethoxy-5-nitroso-6- aminopyrimidine inhibitors of cyclin-dependent kinase 2. Organic and Biomolecular Chemistry 2007, 5(10), 1577-1585.
  • Bettayeb K, Tirado OM, Marionneau-Lambot S, Ferandin Y, Lozach O, Morris JC, Mateo-Lozano S, Drueckes P, Schachtele C, Kubbutat MHG, Liger F, Marquet B, Joseph B, Echalier A, Endicott JA, Notario V, Meijer L. Meriolins, a new class of cell death-inducing kinase inhibitors with enhanced selectivity for cyclin-dependent kinases. Cancer Research 2007, 67(17), 8325-8334.
  • Welburn JPI, Tucker JA, Johnson T, Lindert L, Morgan M, Willis A, Noble MEM, Endicott JA. How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A. Journal of Biological Chemistry 2007, 282(5), 3173-3181.
  • Lowe ED, Hasan N, Trempe JF, Fonso L, Noble MEM, Endicott JA, Johnson LN, Brown NR. Structures of the Dsk2 UBL and UBA domains and their complex. Acta Crystallographica. Section D: Biological Crystallography 2006, 62(2), 177-188.
  • Griffin RJ, Henderson A, Curtin NJ, Echalier A, Endicott J, Hardcastle IR, Newell DR, Noble M, Wang L, Golding BT. Searching for cyclin-dependent kinase inhibitors using a new variant of the cope elimination. Journal of the American Chemical Society 2006, 128(18), 6012-6013.
  • Pratt DJ, Bentley J, Jewsbury P, Boyle FT, Endicott JA, Noble MEM. Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity. Journal of Medicinal Chemistry 2006, 49(18), 5470-5477.
  • Doerig C, Billker O, Pratt D, Endicott J. Protein kinases as targets for antimalarial intervention: Kinomics, structure-based design, transmission-blockade, and targeting host cell enzymes. Biochimica et biophysica acta - Proteins and Proteomics 2005, 1754(1-2), 132–150.
  • MacDonald N, Welburn JPI, Noble MEM, Nguyen A, Yaffe MB, Clynes D, Moggs JG, Orphanides G, Thomson S, Edmunds JW, Clayton AL, Endicott JA, Mahadevan LC. Molecular basis for the recognition of phosphorylated and phosphoacetylated histone H3 by 14-3-3. Molecular Cell 2005, 20(2), 199-211.
  • Trempe JF, Brown NR, Lowe ED, Gordon C, Campbell ID, Noble MEM, Endicott JA. Mechanism of Lys48-linked polyubiquitin chain recognition by the Mud1 UBA domain. EMBO Journal 2005, 24(18), 3178-3189.
  • Noble M, Barrett P, Endicott J, Johnson L, McDonnell J, Robertson G, Zawaira A. Exploiting structural principles to design cyclin-dependent kinase inhibitors. Biochimica et Biophysica Acta: Proteins and Proteomics 2005, 1754(1-2), 58-64.
  • Sasaki T, Funakoshi M, Endicott JA, Kobayashi H. Budding yeast Dsk2 protein forms a homodimer via its C-terminal UBA domain. Biochemical and Biophysical Research Communications 2005, 336(2), 530-535.
  • Hardcastle IR, Arris CE, Bentley J, Boyle FT, Chen Y, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Jewsbury, P., Menyerol, J., Mesguiche, V., Newell, D.R., Noble, M., Pratt, D., Wang, L., Whitfield, H.J. N2-substituted O6-cyclohexylmethylguanine derivatives: Potent inhibitors of cyclin-dependent kinases 1 and 2. Journal of Medicinal Chemistry 2004, 47(15), 3710-3722.
  • Holton S, Merckx A, Burgess D, Doerig C, Noble M, Endicott J. Structures of P-falciparum PfPK5 test the CDK regulation paradigm and suggest mechanisms of small molecule inhibition. Structure 2003, 11(11), 1329-1337.
  • Sayle, K., Bentley, J., Boyle, F., Calvert, A. H., Cheng, Y., Curtin, N. J., Endicott, J., Golding, B., Hardcastle, I., Jewsbury, P., Mesguiche, V., Newell, D. R., Noble, M., Parsons, R., Pratt, D., Wang, L., Griffin, R. J. Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2. Bioorganic and Medicinal Chemistry Letters 2003, 13(18), 3079-3082.
  • Mettey Y, Gompel M, Thomas V, Garnier M, Leost M, Ceballos-Picot I, Noble M, Endicott J, Vierfond JM, Meijer L. Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. Journal of Medicinal Chemistry 2003, 46(2), 222-236.
  • Mesguiche, V, Parsons, R.J., Arris, C.E., Bentley, J., Boyle, F., Curtin, N.J., Davies, T.G., Endicott, J., Gibson, A., Golding, B., Griffin, R.J., Jewsbury, P., Johnson, L.N., Newell, D.R., Noble, M.E.M., Wang, L., Hardcastle, I.R. 4-Alkoxy-2,6-diaminopyrimidine derivatives: Inhibitors of cyclin dependent kinases 1 and 2. Bioorganic and Medicinal Chemistry Letters 2003, 13(2), 217-222.
  • Davies T, Bentley J, Arris CE, Boyle FT, Curtin NJ, Endicott J, Gibson A, Golding BT, Griffin RJ, Hardcastle IR, Jewsbury, P., Johnson, L., Mesguiche, V., Newell, D.R., Noble, M., Tucker, J.A., Wang, L., Whitfield, H.J. Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor. Nature Structural Biology 2002, 9(10), 745-749.
  • Gibson A, Arris CE, Bentley J, Boyle F, Curtin NJ, Davies T, Endicott J, Golding BT, Grant S, Griffin R, Jewsbury, P., Johnson, L., Mesguiche, V., Newell, D.R., Noble, M., Tucker, J., Whitfield, H.J. Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O6-substituted guanine derivatives. Journal of Medicinal Chemistry 2002, 45(16), 3381-3393.
  • Doerig C, Endicott J, Chakrabarti D. Cyclin-dependent kinase homologues of Plasmodium falciparum. International Journal for Parasitology 2002, 32(13), 1575–1585.
  • Davies TG, Tunnah P, Meijer L, Marko D, Eisenbrand G, Endicott JA, Noble MEM. Inhibitor binding to active and inactive CDK2: The crystal structure of CDK2-cyclin A/indirubin-5-sulphonate. Structure 2001, 9(5), 389-397.
  • Lawrie AM, Tito P, Hernandez H, Brown NR, Robinson CV, Endicott JA, Noble MEM, Johnson LN. Xenopus phospho-CDK7/cyclin H expressed in baculoviral-infected insect cells. Protein Expression and Purification 2001, 23(2), 252-260.
  • Bentley J, Arris CE, Boyle FT, Calvert AH, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Grant S, Griffin RJ, Jewsbury PJ, Johnson LN, Noble MEM, Newell DR. Structure-activity relationships and cellular effects of novel purine- and pyrimidine-based cyclin dependent kinase inhibitors. Clinical Cancer Research 2000, 6, 328.
  • Arris CE, Boyle FT, Calvert AH, Curtin NJ, Endicott JA, Garman EF, Gibson AE, Golding BT, Grant S, Griffin RJ, Jewsbury P, Johnson LN, Lawrie AM, Newell DR, Noble MEM, Sausville EA, Schultz R, Yu W. Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. Journal of Medicinal Chemistry 2000, 43(15), 2797-2804.
  • Legraverend M, Tunnah P, Noble M, Ducrot P, Ludwig O, Grierson DS, Leost M, Meijer L, Endicott J. Cyclin-dependent kinase inhibition by new C-2 alkynylated purine derivatives and molecular structure of a CDK2-inhibitor complex. Journal of Medicinal Chemistry 2000, 43(7), 1282-1292.
  • Brown NR, Noble MEM, Endicott JA, Johnson LN. The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. Nature Cell Biology 1999, 1(7), 438-443.
  • Johnson LN, Noble MEM, Barford D, Brown N, Endicott JA, Lawrie A, Owen DJ. Signal transduction proteins: Structural basis of control by phosphorylation. Journal of the Chemical Society of Pakistan 1999, 21(3), 185-201.
  • Hoessel R, Leclerc S, Endicott JA, Noble MEM, Lawrie A, Tunnah P, Leost M, Damiens E, Marie D, Marko D, Niederberger E, Tang WC, Eisenbrand G, Meijer L. Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nature cell biology 1999, 1(1), 60-67.
  • Brown NR, Noble MEM, Lawrie AM, Morris MC, Tunnah P, Divita G, Johnson LN, Endicott JA. Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2 structure and activity. Journal of Biological Chemistry 1999, 274(13), 8746-8756.
  • Endicott JA, Noble MEM, Tucker JA. Cyclin-dependent kinases: inhibition and substrate recognition. Current Opinion in Structural Biology 1999, 9(6), 738-744.
  • Endicott JA, Noble MEM. Structural principles in cell-cycle control: beyond the CDKs. Structure 1998, 6(5), 535-541.
  • Endicott JA, Noble ME, Garman EF, Brown N, Rasmussen B, Nurse P, Johnson LN. The crystal structure of p13suc1, a p34cdc2-interacting cell cycle control protein. EMBO Journal 1995, 14(5), 1004-1014.
  • Brown NR, Noble MEM, Endicott JA, Garman EF, Wakatsuki S, Mitchell E, Rasmussen B, Hunt T, Johnson LN. The crystal structure of Cyclin A. Structure 1995, 3(11), 1235-1247.
  • Endicott JA, Nurse P. The cell cycle and suc1: From structure to function?. Structure 1995, 3(4), 321-325.
  • Bourne Y, Arvai AS, Bernstein SL, Watson MH, Reed SI, Endicott JE, Noble ME, Johnson LN, Tainer JA. Crystal structure of the cell cycle-regulatory protein suc1 reveals a beta-hinge conformational switch. Proceedings of the National Academy of Sciences 1995, 92(22), 10232-10236.
  • Endicott JA, Nurse P, Johnson LN. Mutational analysis supports a structural model for the cell cycle protein kinase p34. Protein Engineering 1994, 7(2), 243-253.
  • Juranka P, Zhang F, Kulpa J, Endicott J, Blight M, Holland IB, Ling V. Characterization of the hemolysin transporter, HlyB, using an epitope insertion. The Journal of biological chemistry 1992, 267(6), 3764-3770.
  • Endicott JA, Sarangi F, Ling V. Complete cDNA sequences encoding the Chinese hamster P-glycoprotein gene family. DNA sequence : the journal of DNA sequencing and mapping 1991, 2(2), 89-101.
  • Endicott JA, Juranka PF, Sarangi F, Gerlach JH, Deuchars KL, Ling V. Simultaneous expression of two P-glycoprotein genes in drug-sensitive Chinese hamster ovary cells. Molecular and Cellular Biology 1987, 7(11), 4075-4081.

• Book Chapter

  • Martin MP, Endicott JA, Noble MEM, Tatum NJ. Crystallographic fragment screening in academic cancer drug discovery. In: Methods in Enzymology. San Diego: Academic Press Inc, 2023, pp.211-234.

• Conference Proceedings (inc. Abstracts)

  • Ahn M, Bevan L, Buck I, Cano C, Castro J, Cons B, Endicott J, Fazal L, Ferrari N, Hardcastle I, Hearn K, Holvey R, Howard S, Johnson C, Jennings C, Kucia-Tran J, Kyle S, Lunec J, Lyons J, Miller D, Rees D, Noble M, Newell DR, Reeks J, Saini H, St Denis J, Tamanini E, Thomas H, Thompson N, Vinkovic M, Ward G, Wallis N, Walton H, Wedge S, Williams P, Willmore E, Wilshire N, Zhao Y, Chessari G. Discovery of ASTX295, a potent, next-generation small molecule antagonist of MDM2 with differentiated pharmacokinetic profile. In: American Association for Cancer Research Annual Meeting. 2024, San Diego: AACR Journals.
  • Massa BC, Martin MP, Noble ME, Endicott JA. Structural and functional characterization of Skp2-containing complexes. In: AACR 106th Annual Meeting 2015. 2015, Philadelphia, USA: American Association for Cancer Research.
  • Martin M, Anscombe E, Meschini E, Staunton D, Geitmann M, Danielson UH, Wang LZ, Vidal RM, Reuillon T, Golding BT, Newell DR, Wedge S, Noble MEM, Endicott JA, Griffin RJ. Identification and characterization of an irreversible inhibitor of CDK2. In: 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. 2014, Barcelona, Spain: Elsevier.
  • Shouksmith AE, Evans LE, Griffin RJ, Golding BT, Newell H, Miller DC, Noble MEM, Endicott JA, Tweddle D. Design and synthesis of putative small-molecule inhibitors targeting the SCFSKP2 E3 ligase complex. In: 247th ACS National Meeting and Exposition. 2014, Dallas, Texas: American Chemical Society.
  • Lebraud H, Golding BT, Meschini E, Cano C, Anscombe E, Wang LZ, Endicott JA, Noble MEM, Newell DR, Griffin RJ. Anticancer agents targeted against cyclin-dependent kinase 2 (CDK2): Structure-based design of irreversible and reversible inhibitors. In: 247th ACS National Meeting and Exposition. 2014, Dallas, Texas: American Chemical Society.
  • Anil B, Blackburn E, Blackburn T, Cully S, Liu J, Drummond CJ, Endicott JA, Golding BT, Griffin RJ, Haggerty K, Lunec J, Newell DR, Revill CH, Riedinger C, Watson AF, Xu Q, Zhao Y, Hardcastle IR, Noble MEM. An X-ray crystal structure-based understanding of the inhibition of the MDM2-p53 protein-protein interaction by isoindolinones. In: 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. 2014, Barcelona, Spain: Elsevier.
  • Shao H, Abbas AY, Shi S, Foley D, Huang S, Bradshaw TD, Pepper C, Endicott JA, Wang S, Fischer PM. Synthesis and in Vitro Evaluation of Selective CDK9 Inhibitors. In: 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. 2012, Dublin, Ireland: Pergamon.
  • Echalier A, Endicott JA, Noble MEM. Recent developments in cyclin-dependent kinase biochemical and structural studies. In: BBA - Proteins and Proteomics: 6th International Conference on Inhibitors of Protein Kinases (IPK). 2010, Warsaw, Poland: Elsevier BV.
  • Meschini E, Endicott JA, Golding BT, Hardcastle IR, Newell DR, Noble MEM, Wang LZ, Griffin RJ. Design and synthesis of dual CDK2 and CDK7 inhibitors. In: Abstracts of Papers of the American Chemical Society. 2010, American Chemical Society.
  • Echalier A, Endicott JA, Johnson LN, McDonnell J, Noble MEM. Structure-based protein kinase inhibitor design. In: European Journal of Pharmaceutical Sciences: 18th Helsinki Drug Research. 2006, Helsinki, Finland: Elsevier BV.
  • Endicott JA, Merckx A, Hofmann G, Noble MEM. Molecular recognition of indigoids. In: International Meeting on Indirubin, the Red Shade of Indigo. 2003, Musée National de Préhistoire, Les Eyzies-de-Tayac, France: Editions "Life in Progress".
  • Davies TG, Pratt DJ, Endicott JA, Johnson LN, Noble MEM. Structure-based design of cyclin-dependent kinase inhibitors. In: Pharmacology & Therapeutics: 2nd International Confernce on Inhbitors of Protein Kinases. 2002, Warsaw, Poland: Elsevier Inc.
  • Johnson LN, DeMoliner E, Brown NR, Song HW, Barford D, Endicott JA, Noble MEM. Structural studies with inhibitors of the cell cycle regulatory kinase cyclin-dependent protein kinase 2. In: Pharmacology & Therapeutics: 2nd International Confernce on Inhbitors of Protein Kinases. 2002, Warsaw, Poland: Elsevier Inc.
  • Sayle KL, Mesguishe V, Parsons RJ, Bentley J, Davies TG, Endicott JA, Noble MEM, Wang LZ, Hardcastle IR, Golding BT. 4-Alkoxy-2,6-diaminopyrimidine derivatives: inhibitors of cyclin dependent kinases 1 and 2. In: European Journal of Cancer: 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics. 2002, Frankfurt, Germany: Pergamon.
  • Noble MEM, Endicott JA. Chemical inhibitors of cyclin-dependent kinases: Insights into design from X-ray crystallographic studies. In: Pharmacology & Therapeutics: 1st International Conference on Inhibitors of Protein Kinases (IPK). 1999, Warsaw, Poland: Elsevier Inc.
  • Grant S, Boyle F, Calvert AH, Curtin NJ, Endicott J, Golding BT, Griffin RJ, Johnson LN, Newell DR, Noble MEM, Robson CN. O-6-alkylguanines as selective inhibitors of cyclin dependent kinases. In: 10th NCI-EORTC Symposium on New Drugs in Cancer Therapy. 1998, Amsterdam, The Netherlands: Annals of Oncology: Oxford University Press.
  • Endicott J, Noble M, Lawrie A, Tunnah P, Brown N, Johnson L, Calvert AH, Curtin NJ, Golding BT, Griffin RJ, Newell DR. Insights into CDK inhibitor design from X-ray crystallographic studies. In: 10th NCI-EORTC Symposium on New Drugs in Cancer Therapy. 1998, Amsterdam, The Netherlands: Annals of Oncology: Oxford University Press.
  • Johnson LN, Brown NR, Endicott JA, Lawrie AM, Lowe ED, Noble MEM, Tunnah P. The structural basis for control by phosphorylation. In: FASEB Journal. 1997, Federation of American Societies for Experimental Biology.

• Editorial

  • Trempe JF, Endicott JA. Structural biology - Pass the protein. Nature 2007, 445(7126), 375-376.

• Letters

  • Lawrie AM, Noble MEM, Tunnah P, Brown NR, Johnson LN, Endicott JA. Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2. Nature Structural Biology 1997, 4(10), 796-801.
  • Gerlach JH, Endicott JA, Juranka PF, Henderson G, Sarangi F, Deuchars KL, Ling V. Homology between P-glycoprotein and a bacterial haemolysin transport protein suggests a model for multidrug resistance. Nature 1986, 324(6096), 485-489.

• Reviews

  • Hope I, Endicott JA, Watt JE. Emerging approaches to CDK inhibitor development, a structural perspective. RSC Chemical Biology 2023, 4(2), 146-164.
  • Wood DJ, Endicott JA. Structural insights into the functional diversity of the CDK–cyclin family. Open Biology 2018, 8(9), 180112.
  • Endicott JA, Noble MEM, Johnson LN. The Structural Basis for Control of Eukaryotic Protein Kinases. Annual Review of Biochemistry 2012, 81, 587-613.
  • Welburn JPI, Endicott JA. Inhibition of the cell cycle with chemical inhibitors: A targeted approach. Seminars in Cell & Developmental Biology 2005, 16(3), 369-381.
  • Pratt DJ, Endicott JA, Noble MEM. The role of structure in kinase-targeted inhibitor design. Current Opinion In Drug Discovery & Development 2004, 7(4), 428-436.
  • Noble MEM, Endicott JA, Johnson LN. Protein kinase inhibitors: Insights into drug design from structure. Science 2004, 303(5665), 1800-1805.
  • Noble MEM, Endicott JA, Brown NR, Johnson LN. The cyclin box fold: protein recognition in cell-cycle and transcription control. Trends in Biochemical Sciences 1997, 22(12), 482-487.
  • Endicott JA, Ling V. The Biochemistry of P-Glycoprotein-Mediated Multidrug Resistance. Annual Review of Biochemistry 1989, 58, 137-171.