Projects per year
Key achievements over last 5 years:
Validation of N-myristoyltransferase as a drug target in human African trypanosomiasis and development of compounds which are potential candidates for stage 1 disease.
1. Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors. Brand, S.; Cleghorn, L. A. T.; McElroy, S. P.; Robinson, D. A.; Smith, V. C.; Hallyburton, I.; Harrison, J. R.; Norcross, N. R.; Norval, S.; Spinks, S.; Stojanovski, L.; Torrie, L. S.; Frearson, J. A.; Brenk, R.; Fairlamb, A. H.; Ferguson, M. A. J.; Read, K. D.; Wyatt, P. G.; Gilbert, I. H. J. Med. Chem. 2012, 55, 140-152.
2. N-myristoyltransferase inhibitors as new leads to treat sleeping sickness. Frearson, J. A.; Brand, S.; McElroy, S. P.; Cleghorn, L. A. T.; Smid, O.; Stojanovski, L.; Price, H. P.; Guther, M. L. S.; Torrie, L. S.; Robinson, D. A.; Hallyburton, I.; Mpamhanga, C. P.; Brannigan, J. A.; Wilkinson, A. J.; Hodgkinson, M.; Hui, R.; Qiu, W.; Raimi, O. G.; Van Aalten, D. M. F.; Brenk, R.; Gilbert, I. H.; Read, K. D.; Fairlamb, A. H.; Ferguson, M. A. J.; Smith, D. F.; Wyatt, P. G. Nature, 2010, 464, 728-732.
Development of potential preclinical candidates for African animal trypanosomiasis.
Development of compounds to late leads status for malaria.
Key player in redefining CNS drug discovery lead optimization process.
Central nervous system drug disposition: The relationship between in situ brain permeability and brain free fraction. Summerfield S, Read KD, Begley DJ, Obradovic T, Hidalgo IJ, Coggon S, Lewis AV, Porter RA and Jeffrey P. (2007). JPET 322, 205-213
Receptor occupancy and brain free fraction. Watson JM, Wright S, Lucas A, Clarke KL, Viggers J, Cheetham S, Jeffrey P, Porter RA and Read KD (2009). Drug Metabolism and Disposition 37, 753-760
Assessing brain free fraction in early drug discovery. Read KD and Braggio S (2010). Expert Opin. Drug Metab. Toxicol. 6 (3), 337-344
Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs. Gunn RN, Summerfield SG, Salinas CA, Read KD, Guo Q, Searle GE, Parker CA, Jeffrey P, Laruelle M (2012). J. Cereb Blood Flow Metab. 32(5):874-83
The Anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis. Wyllie S, Patterson S, Stojanovski L, Simeons FRC, Norval S, Kime R, Read KD and Fairlamb AH (2012). Science Translational Medicine, 4, 1-7
Grants awarded over last 5 years:
GALVmed, April 2012 to August 2013; £398K. Discovery and development of new drugs for treatment/ prevention of Trypanosomiasis in cattle. PIs Kevin Read and Ian Gilbert
Scottish funding council and TPP Global Development Ltd. Jobs, health and wealth. November 2011 to September 2013. PIs: Paul Wyatt, David Gray, Kevin Read, Andrew Hopkins. Full award value: £825,000
Wellcome Trust; April 2011 to March 2016; £8.6M; Drug Discovery for Tropical Diseases; PIs: Paul Wyatt, Michael Ferguson and Alan Fairlamb; Co-applicants: Daan van Aalten, Ian Gilbert, Ruth Brenk, Kevin Read. Wellcome Trust Reference 092340.
Drug Discovery for Mycobacterium tuberculosis; 1st March 2011 to 28th February 2014. PI: Paul Wyatt; Co-applicants Ian Gilbert, Kevin Read. Funded in part by a Grant from the Foundation for the National Institutes of Health with support from the Bill and Melinda Gates Foundation. Total consortium grant $6,781,984. Dundee component £770,248
Medicines for Malaria Venture; Discovery and Optimisation of Phenotypic Hits; 1st April 2010 to 31st December 2013. US$1,636,000. PIs: Ian Gilbert and Kevin Read; Coapplicants: Alan Fairlamb, David Gray, Paul Wyatt.
MRC DPFS devolved portfolio. The Development of N-Myristoyl transferase Inhibitors as Anticancer Agents. April 2010 to March 2011. Paul Wyatt (PI), co-applicants: Kevin Read, Alastair Thompson, David Blake (Cyclacel). Full award value: £255,744
MRC DPFS devolved portfolio. Translating a Portfolio of Novel Biological Targets towards Therapeutics. 1st October 2009 to 30th September 2011. PI: Paul Wyatt. Co-applicant Kevin Read. Full award value: £1,087,071
Drugs for Neglected Diseases inititiative; Identification of Drug Candidates to Treat Leishmaniasis; 1st April 2009 to 31st March 2014; £1,810,000. PI: Paul G. Wyatt; Co-applicants, A.H. Fairlamb, I.H. Gilbert, K.D. Read.
European Union; Jan 2009 to June 2012; total grant €2.6M/ Dundee component €508K; Nucleobase derivatives as drugs against trypanosomal diseases (Trypobase). Partners Consejo Superior da Investigaciones Cientificas (coordinator), University of Dundee, Medivir, University of York, Swiss Tropical Institute, Syngene, Institute Pasteur Montevideo.
I have over 22 years of experience working in the pharmaceutical industry as a DMPK scientist, 16 years of which have been in CNS drug discovery. My first degree in applied biology was obtained from Coventry polytechnic and my PhD (evaluation of blood-brain barrier models for measurement and prediction of brain drug penetration) was obtained from Kings College, London.
I started my career in 1989 as a DMPK scientist with Huntingdon Research centre gaining experience in the use of radionuclides in drug metabolism studies and carrying out ADME and PK studies in pre-clinical species in support of various drug development projects. In 1992 I joined the DMPK division in Glaxo Group Research in the UK, gaining extensive experience in drug discovery support. This involved optimisation of new chemical entities emerging from the projects with respect to their in vitro/in vivo metabolic stability, absorption, blood-brain barrier penetration and pharmacokinetic/pharmacodynamic profiles.
In 1996 I became a core member of a multi-disciplinary and multi-national research team within GlaxoWellcome, responsible for the development, evaluation and implementation of appropriate technologies to ensure “efficacious” penetration of the CNS. I helped lead this group and had a pivotal role in setting strategy, generating data and bringing knowledge to bear in all CNS drug discovery projects.
In 2001 I moved to GlaxoSmithKline, Italy as a Research Leader with management responsibility for 9 graduate and post-graduate scientists. I was responsible for the establishment of an in vitro DMPK laboratory with capacity to support all Verona, Italy and Harlow, UK, Psychiatry CEDD exploratory and lead optimisation (LO) programmes. A number of assays were developed and implemented, including CYP inhibition, metabolism dependent inhibition, intrinsic clearance, reactive metabolite assessment (GSH trapping assay), reaction phenotyping, tissue and protein binding and a Pgp substrate assay. I was accountable for high quality, rapid in vitro support to all drug discovery programmes within the Psychiatry CEDD, UK and Italy.
In April 2004 I was promoted to Senior Research Leader and my responsibility shifted from the in vitro team to manage the DMPK lead optimisation team. I had management responsibility for 8 scientists, accountable for strategy and co-ordination of all DMPK support to all Verona CNS drug discovery LO programmes.
I was a GSK programme leader for a full lead optimisation programme up to candidate selection in major depressive disorder and a deputy programme leader on two other psychiatry LO programmes from 2004 through end 2007.
In January 2008, I moved to the School of Life Sciences, University of Dundee, to establish a DMPK group. I have now recruited six scientists and implemented industry standard assays coupled with state of the art UPLCMSMS technology for supporting hit to lead and lead optimisation programmes. The capabilities now available at Dundee include in silico ADME models together with a range of in vitro and in vivo tools, selected in order to provide a good overall assessment of the developability profile of compounds early in the lead optimisation process.
A scaffold-hopping strategy on a series of proteasome inhibitors which led to a preclinical candidate for the treatment of visceral leishmaniasisThomas, M., Brand, S., De Rycker, M., Zuccotto, F., Lukac, I., Dodd, P., Ko, E-J., Manthri, S., McGonagle, K., Osuna-Cabello, M., Riley, J., Pont, C., Simeons, F., Stojanovski, L., Thomas, J., Thompson, S., Viayna, E., Fiandor, J. M., Martín, J., Wyatt, P. G. & 4 others, , 27 Apr 2021, (E-pub ahead of print) In: Journal of Medicinal Chemistry. 26 p.
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile
A Systematic Study of the In Vitro Pharmacokinetics and Estimated Human In Vivo Clearance of Indole and Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists Detected on the Illicit Drug MarketBrandon, A. M., Antonides, L. H., Riley, J., Epemolu, O., McKeown, D. A., Read, K. D. & McKenzie, C., 5 Mar 2021, In: Molecules. 26, 5, 26 p., 1396.
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile12 Downloads (Pure)
Spirocycle MmpL3 Inhibitors with Improved hERG and Cytotoxicity Profiles as Inhibitors of Mycobacterium tuberculosis GrowthRay, P. C., Huggett, M., Turner, P. A., Taylor, M., Cleghorn, L. A. T., Early, J., Kumar, A., Bonnett, S. A., Flint, L., Joerss, D., Johnson, J., Korkegian, A., Mullen, S., Moure, A. L., Davis, S. H., Murugesan, D., Mathieson, M., Caldwell, N., Engelhart, C. A., Schnappinger, D. & 17 others, , 26 Jan 2021, In: ACS Omega. 6, 3, p. 2284-2311 28 p.
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile8 Downloads (Pure)
Discovery and Optimization of a Compound Series Active against Trypanosoma cruzi, the Causative Agent of Chagas DiseaseHarrison, J. R., Sarkar, S., Hampton, S., Riley, J., Stojanovski, L., Sahlberg, C., Appelqvist, P., Erath, J., Mathan, V., Rodriguez, A., Kaiser, M., Pacanowska, D. G., Read, K. D., Johansson, N. G. & Gilbert, I. H., 26 Mar 2020, In: Journal of Medicinal Chemistry. 63, 6, p. 3066-3089 24 p.
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile12 Downloads (Pure)
Identification and Optimization of a Series of 8-Hydroxy Naphthyridines with Potent In Vitro Antileishmanial Activity: Initial SAR and Assessment of In Vivo ActivityThomas, M., De Rycker, M., Wall, R. J., Spinks, D., Epemolu, O., Manthri, S., Norval, S., Osuna-Cabello, M., Patterson, S., Riley, J., Simeons, F. R. C., Stojanovski, L., Thomas, J., Thompson, S., Naylor, C., Fiandor, J. M., Wyatt, P. G., Marco, M., Wyllie, S., Read, K. D. & 2 others, , 10 Sep 2020, In: Journal of Medicinal Chemistry. 63, 17, p. 9523-9539 17 p.
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile1 Citation (Scopus)13 Downloads (Pure)
Supporting data for “A Systematic Study of the In Vitro Pharmacokinetics and Estimated Human In Vivo Clearance of Indole and Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists Detected on the Illicit Drug Market”
Matthew Jarron (Organiser), Amy Cameron (Organiser), Nicola Morrice (Contributor), Chim Lang (Contributor), Agathe Lermant (Contributor), Cara Nicholson (Contributor), Colin Henderson (Contributor), Ros Langston (Member), Laureano de la Vega (Member), Gillian Smith (Contributor), Daniella Cavellini (Contributor), Andrew Evans (Contributor), Jane Dickson (Contributor), Jacqueline Eccles (Contributor), Ola Epemolu (Contributor), Kevin Read (Contributor), Mattie Pawlowic (Contributor), Matthew Taylor (Contributor), Sarah McKim (Contributor), Henry McSorley (Contributor), Peter Mossey (Contributor), Susan Wyllie (Contributor), Niamh Nic Daeid (Contributor), Seaneen McDougall (Contributor), Ailsa Mackintosh (Contributor), Ali Floyd (Contributor), Catharine Goddard (Contributor), Li Kang (Contributor), James Gemmill (Contributor) & Rolf Black (Contributor)Nov 2020
Activity: Other activity types › Other
Jonathan Urch (Organiser), Lynn Kilbride (Presenter), Jacob George (Presenter), Brenda Keatch (Presenter), Nick Hopkins (Presenter), Victoria Cowling (Presenter), Qi Zhao (Presenter), Cameron Ross (Presenter), Samia Khan (Presenter), David Keeble (Presenter), Nicholas Fyfe (Presenter), Aliki Varvogli (Presenter), Anja Johansen (Presenter), Kevin Read (Presenter), Maggie Bartlett (Presenter), Jason Nelson (Presenter), Raphael Heffron (Presenter), Lesley Colvin (Presenter), Simon Arthur (Presenter), Volker Röben (Presenter), James Chalmers (Presenter), Leanne Wallace (Organiser), Niamh Nic Daeid (Presenter), Bob Steele (Presenter), Annie Anderson (Presenter), Andrew Atherton (Chair), Wendy Alexander (Chair) & John Rowan (Chair)9 Jan 2019 → 11 Jan 2019
Activity: Other activity types › Public engagement and outreach - public lecture/debate/seminarFile
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