Staff Profile

Background

After gaining an undergraduate degree in Biochemistry and Biological Chemistry from the University of Nottingham, I took up a position in the Discovery Chemistry department of the Pfizer Sandwich labs. I worked across multiple therapeutic areas, including cardiovascular, pain and sexual health. In 2002 I progressed to a medicinal chemistry team leader position, and subsequently assumed a Design Lead role, having responsibility and accountability for medicinal chemistry strategy and delivery on a key project. In 2011 I took up the opportunity of a three year secondment as a visiting researcher at Newcastle University to work with Professor Roger Griffin in the Newcastle Cancer Centre,  prosecuting new and challenging targets with the aim of developing new chemical tools for the validation of novel biological targets for cancer treatment. I subsequently assumed a role as a Senior Research Associate in the Newcastle Cancer Centre. I have extensive experience of designing compounds across target classes including protein-protein interaction inhibitors, bromodomain ligands, reversible and irreversible kinase inhibitors, centrally active GPCR agonists & antagonists, ion channel modulators, and enzyme inhibitors.

SCOPUS: Click here.

The design and synthesis of novel probe molecules for validation of anti-cancer targets, and for lead optimisation studies.

Fragment based drug discovery.

Structure-based drug design.

Molecular-property-based drug design

• Articles

  • 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.
  • Chessari G, Hardcastle IR, Ahn JS, Anil B, Anscome E, Bawn RH, Bevan LD, Blackburn TJ, Buck I, Cano C, Carbain B, Castro J, Cons B, Cully SJ, St Denis J, Endicott JA, Fazal L, Golding BT, Griffin RJ, Haggerty K, Harnor S, Hearn K, Hobson S, Holvey RS, Howard S, Jennings C, Johnson CN, Lunec J, Miller DC, Newell DR, Noble MEM, Reeks J, Revill CH, Riedinger C, Tamanini E, Thomas H, Thompson NT, Vinkovic M, Wedge SR, Williams PA, Wilsher N, Zhang B, Zhao Y. Structure-Based Design of Potent and Orally Active Isoindolinone Inhibitors of MDM2-p53 Protein–Protein Interaction. Journal of Medicinal Chemistry 2021, 64(7), 4071-4088.
  • 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.
  • Brown AD, Bagal SK, Blackwell P, Blakemore DC, Brown B, Bungay PJ, Corless M, Crawforth J, Fengas D, Fenwick DR, Gray V, Kenp M, Klute W, Malet-Sainz L, Miller D, Murata YC, Payne E, Skerratt S, Warmus JS. The discovery and optimization of benzimidazoles as selective Na_V1.8 blockers for the treatment of pain. Bioorganic & Medicinal Chemistry 2019, 27(1), 230-239.
  • 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.
  • 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.
  • Bagal SK, Kemp M, Bungay P, Hay T, Murata Y, Payne E, Stevens E, Brown A, Blakemore DC, Corbett M, Miller DC, Omoto K, Warmus JS. Discovery and optimisation of potent and highly subtype selective Na_v1.8 inhibitors with reduced cardiovascular liabilities. MedChemComm 2016, 7(10), 1925-1931.
  • Reuillon T, Alhasan SF, Beale GS, Bertoli A, Brennan A, Cano C, Reeves HL, Newell DR, Golding BT, Miller DC, Griffin RJ. Design and synthesis of biphenyl and biphenyl ether inhibitors of sulfatases. Chemical Science 2016, 7(4), 2821-2826.
  • Shouksmith AE, Evans LE, Tweddle DA, Miller DC, Willmore E, Newell DR, Golding BT, Griffin RJ. Synthesis and Activity of Putative Small-​Molecule Inhibitors of the F-​Box Protein SKP2. Australian Journal of Chemistry 2015, 68(4), 660-679.
  • Miller DC, Carbain B, Beale GS, Alhasan SF, Reeves HL, Baisch U, Newell DR, Golding BT, Griffin RJ. Regioselective sulfamoylation at low temperature enables concise syntheses of putative small molecule inhibitors of sulfatases. Organic & Biomolecular Chemistry 2015, 13(18), 5279-5284.
  • Mills JEJ, Brown AD, Ryckmans T, Miller DC, Skerratt SE, Barker CM, Bunnage ME. SAR mining and its application to the design of TRPA1 antagonists. MedChemComm 2012, 4, 174-178.
  • Miller DC, Lunn G, Jones P, Sabnis Y, Davies NL, Driscoll P. Investigation of the effect of molecular properties on the binding kinetics of a ligand to its biological target. MedChemComm 2012, 3(4), 449-452.
  • Reuillon T, Bertoli A, Griffin RJ, Miller DC, Golding BT. Efficacious N-protection of O-aryl sulfamates with 2,4-dimethoxybenzyl groups. Organic & Biomolecular Chemistry 2012, 10(37), 7610-7617.
  • Miller DC, Klute W, Brown AD. Discovery of potent, metabolically stable purine CRF-​1 antagonists with differentiated binding kinetic profiles. Bioorg. Med. Chem. Lett 2011, 21, 6108-6111.
  • Miller DC, Klute W, Calabrese A, Brown AD. Optimising metabolic stability in lipophilic chemical space: The identification of a metabolically stable pyrazolopyrimidine CRF-​1 receptor antagonist. Bioorg. Med. Chem. Lett 2009, 19, 6144-6147.
  • Fish PV, MacKenny M, Bish G, Buxton T, Cave R, Drouard D, Hoople D, Jessiman A, Miller D, Pasquinet C. Enantioselective synthesis of (R)​- and (S)​-​N-​Boc-​morpholine-​2-​carboxylic acids by enzyme-​catalyzed kinetic resolution: application to the synthesis of reboxetine analogs. Tetrahedron Letters 2009, 50, 389-391.
  • Bunnage ME, Mathias JP, Wood A, Miller D, Street SDA. Highly potent and selective chiral inhibitors of PDE5: An illustration of Pfeiffer's rule. Bioorg. Med. Chem. Lett 2008, 18, 6033-6036.
  • Bunnage ME, Blagg J, Steele J, Owen DR, Allerton C, McElroy AB, Miller D, Ringer T, Butcher K, Beaumont K. Discovery of potent and selective inhibitors of activated thrombin-​activatable fibrinolysis inhibitor for the treatment of thrombosis. J. Med. Chem 2007, 50, 6095-6103.

• Book Chapters

  • Bordoni C, Brough DJ, Davison G, Hunter JH, Lopez-Fernandez JD, McAdam K, Miller DC, Morese PA, Papaioannou A, Uguen M, Ratcliffe P, Sitnikov N, Waring MJ. Cardiac Ion Channel Inhibition. In: Schnider P, ed. The Medicinal Chemist’s Guide to Solving ADMET Challenges. Cambridge: Royal Society of Chemistry, 2021, pp.403-492.
  • Waring MJ, Leach AG, Miller DC. Challenges in the Medicinal Chemical Optimization of Binding Kinetics. In: Thermodynamics and Kinetics of Drug Binding. Wiley Blackwell, 2015, pp.191-210.

• Conference Proceedings (inc. Abstracts)

  • Willmore E, Ahn M, Bevan L, Kyle S, Zhao Y, Thomas H, Rankin KS, Bevan L, Fazal L, Hearn K, Wilsher N, Kucia-Tran J, Ferrari N, Wallis N, Thompson N, Lyons J, Miller D, Cano C, Noble M, Hardcastle I, Howard S, Chessari G, Lunec J, Newell DR, Wedge S. Targeting the MDM2-p53 interaction: Time- and concentration-dependent studies in tumor and normal human bone marrow cells reveal strategies for an enhanced therapeutic index. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024. 2024, San Diego, California: AACR.
  • 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.
  • Hepworth D, Cook A, Blagg J, Allerton C, Miller D, Baxter A. Optimization of oral pharmacokinetics in the discovery of clinical candidates for the treatment of sexual dysfunction. In: 237th ACS National Meeting, March 22-26, 2009. 2009, Salt Lake City, UT, United States.

• Patents

  • Chessari G, Howard S, Buck IM, Cons BD, Johnson CN, Holvey RS, Rees DC, StDenis JD, Tamanini E, Golding BT, Hardcastle IR, Cano CF, Miller DC, Noble MEM, Osborne JD, Peach J, Lewis A, Hirst KL, Whittaker BP, Watson DW, Mitchell DR, Griffin RJ. Preparation of isoindolinones as inhibitors of the MDM2-​p53 interaction having anticancer activity;WO 2017055860. WO2017055860, 2017.
  • Chessari G, Howard S, Buck IM, Cons BD, Johnson CN, Holvey RS, Rees DC, StDenis JD, Tamanini E, Golding BT, Hardcastle IR, Cano CF, Miller DC, Noble MEM, Osborne JD, Peach J, Lewis A, Hirst KL, Whittaker BP, Watson DW, Mitchell DR, Griffin RJ. Preparation of isoindolinones as inhibitors of the MDM2-​p53 interaction having anticancer activity. WO/2017055859, 06/04/2017.
  • Chessari G, Howard S, Buck IM, Cons BD, Johnson CN, Holvey RS, Rees DC, St Denis JD, Tamanini E, Golding BT, Hardcastle IR, Cano CF, Miller DC, Noble MEM, Griffin RJ, Osborne JD, Peach J, Lewis A, Hirst KL, Whittaker BP, Watson DR. ISOINDOLINONE INHIBITORS OF THE MDM2-P53 INTERACTION HAVING ANTICANCER ACTIVITY. PCT/GB2016/053041, 06/04/2017.
  • Reuillon T, Miller D, Myers S, Molyneux L, Cano C, Hardcastle I, Griffin R, Rigoreau L, Golding B, Noble M. Pyrrolcarboxamide Derivatives for the Inhibition of ERK5. WO/2016/042341, 24/03/2016.
  • Bagal SK, Kemp MI, Miller DC, Murata Y. Imidazoles as Nav1.8 inhibitors and their preparation and use in the treatment of pain. USA, WO 2013061205 A2, 2013, 27/03/2014.
  • Bagal SK, Brown AD, Kemp MI, Klute W, Marron BE, Miller DC, Skerratt SE, Suto MJ, West CW, Malet-Sanz L. Benzimidazole and imidazopyridine derivatives as Nav1.8 inhibitors and their preparation and use in the treatment of pain. USA, WO 2013114250, 08/08/2013.
  • Green SP, Lazzari OA, Miller DC, Salingue FH. Salt form of dopamine agonist. US 7,498,329, 2009.
  • Brown AD, Klute W, Miller DC. Preparation of substituted purine compounds as CRF1 receptor antagonists. WO 2009144632, 2009.
  • Cook AS, Miller DC. Preparation of chromanamine compounds as selective dopamine D3 receptor agonists for the treatment of sexual dysfunction. WO 2006056850, 2006.
  • Hepworth D, Jones LH, Miller DC. Preparation of 3-​(1-​carbamoylcyclohexyl)​propionic acid derivatives as inhibitors of neutral endopeptidase enzyme. WO 2006027680, 2006.
  • Green SP, Lazzari OA, Miller DC, Salingue FH. Preparation of [(2R,​5S)​-​5-​methyl-​4-​propylmorpholin-​2-​yl]​pyridin-​2-​amine di-​(S)​-​camphorsulfonate for treatment of sexual dysfunction and neurological disorders. WO 2006082511, 2006.
  • Allerton CMN, Hepworth D, Miller DC. Preparation of indazoles and indolones as dopamine D3 agonists for treatment of sexual dysfunction. US 20050267096, 2005.
  • Allerton CMN, Cook AS, Hepworth D, Miller DC. Aminopyridine derivatives as selective dopamine D3 agonists, their preparation, pharmaceutical compositions, and use in therapy. WO 2005115985, 2005.

• Review

  • Miller DC, Harnor SJ, Martin MP, Noble RA, Wedge SR, Cano C. Modulation of ERK5 Activity as a Therapeutic Anti-Cancer Strategy. Journal of Medicinal Chemistry 2023, 66(7), 4491-4502.