Senior Research Associate
After gaining an undergraduate degree in Biochemistry and Biological Chemistry from the University of Nottingham in 1993, 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 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. On the closure of the Pfizer Sandwich site I 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.
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
- 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, 31/03/2017.
- 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 2017055860. WO2017055860, 2017. In Preparation.
- 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.
- 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 Nav1.8 inhibitors with reduced cardiovascular liabilities. MedChemComm 2016, 7(10), 1925-1931.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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, 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.
- 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, 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.
- 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.
- 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.
- 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.
- Brown AD, Klute W, Miller DC. Preparation of substituted purine compounds as CRF1 receptor antagonists. WO 2009144632, 2009.
- 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.
- 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.
- Hepworth D, Jones LH, Miller DC. Preparation of 3-(1-carbamoylcyclohexyl)propionic acid derivatives as inhibitors of neutral endopeptidase enzyme. WO 2006027680, 2006.
- Cook AS, Miller DC. Preparation of chromanamine compounds as selective dopamine D3 receptor agonists for the treatment of sexual dysfunction. WO 2006056850, 2006.
- 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.
- Allerton CMN, Hepworth D, Miller DC. Preparation of indazoles and indolones as dopamine D3 agonists for treatment of sexual dysfunction. US 20050267096, 2005.