Projects per year
With substantial input into all drug discovery projects in the DDU, I have a strong track record of success in delivery of high quality drug candidates. Since moving to the DDU, notable examples include:
Validation of N-myristoyltransferase as a drug target in human African trypanosomiasis and development of compounds which are potential preclinical candidates for stage 1 only or stage 1 and stage 2 disease. One of these late leads has been subsequently re-purposed into cancer and is currently in Phase 1 clinical trials.
- Frearson, J. A., Brand, S., McElroy, S. P., Cleghorn, L. A., Smid, O., Stojanovski, L., Price, H. P., Guther, M. L., 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., Brenk, R., Gilbert, I. H., Read, K.D., Fairlamb, A. H., Ferguson, M. A., Smith, D. F. and Wyatt, P.G. (2010) N-myristoyltransferase inhibitors as new leads to treat sleeping sickness. Nature. 464, 728-732
- Brand, S., Norcross, N.R, Thompson, S., Harrison, J.R., Smith, V.C., Robinson, D.A., Torrie, L.S., McElroy, S.P., Hallyburton, I., Norval, S., Scullion, P., Stojanovski, L., Simeons, F.R.C., van Aalten, D., Frearson, J.A., Brenk, R., Fairlamb, A.H., Ferguson, M.A.J., Wyatt, P.G., Gilbert, H. and Read, K.D. (2014). Lead Optimization of a Pyrazole Sulfonamide Series of Trypanosoma brucei N-Myristoyltransferase Inhibitors: Identification and Evaluation of CNS Penetrant Compounds as Potential Treatments for Stage 2 Human African Trypanosomiasis. J. Med.Chem. 57, 9855-9869
- Beauchamp E, Yap MC, Iyer A, Perinpanayagam MA, Gamma JM, Vincent KM, Lakshmanan M, Raju A, Tergaonkar V, Tan SY, Lim ST, Dong WF, Postovit LM, Read KD, Gray DW, Wyatt PG, Mackey JR, Berthiaume LG (2020). Targeting N-myristoylation for therapy of B-cell lymphomas. Nature Communications, 11, 5348.
Identifying that the Anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis (VL). As a direct consequence of this jointly published work with Alan Fairlambs laboratory, the Drugs for Neglected Diseases initiative (DNDi) initiated phase II clinical trials for VL in Africa.
- Wyllie, S., Patterson, S., Stojanovski, L., Simeons, F. R., Norval, S., Kime, R., Read, K. D. and Fairlamb, A.H. (2012) The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis. Sci Transl Med. 4, 1-7
Co-leading the malaria programme team that delivered the first preclinical development candidate for the DDU in October 2013. (DDD498; www.mmv.org/research-development/rd-portfolio). MMV project of the year 2014. Currently starting Phase II clinical trials.
- Baragaña, B., Hallyburton, I., Lee, M. C… 57 other authors, Fidock, D.A., Read, K.D., Gilbert, I.H. (2015) A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature, 522, 315-320
- Baragaña B, Norcross NR, Wilson C, Porzelle A, Hallyburton I, Grimaldi R, Osuna-Cabello M, Norval S, Riley J, Stojanovski L, Simeons FRC, Wyatt P, Delves MJ, Meister S, Duff S, Avery VM, Winzeler EA, Sinden RE, Wittlin S, Frearson JA, Gray DW, Fairlamb AH, Waterson D, Campbell SF, Willis P, Read KD and Gilbert IH (2016). Discovery of a Quinoline-4-carboxamide Derivative with a Novel Mechanism of Action, Multistage Antimalarial Activity, and Potent in Vivo Efficacy. J. Med. Chem., 59, 9672-9685.
Co-leading the visceral leishmaniasis drug discovery programme in partnership with GSK. This delivered two preclinical development candidates with differing modes of action. The first entered phase I clinical trials in April 2019 and the second in October 2021.
- Wyllie S, Thomas M, Patterson S, Crouch S, De Rycker M, Lowe R, Gresham, S, Urbaniak MD, Otto TD, Stojanovski L, Simeons FRC, Manthri S, MacLean LM, Zuccotto F, Homeyer N, Pflaumer H, Boesche M, Sastry L, Connolly P, Albrecht S, Berriman M, Drewes G, Gray DW, Ghidelli-Disse S, Dixon S, Fiandor JM, Wyatt PG, Ferguson MAJ, Fairlamb AH, Miles TJ, Read KD and Gilbert IH (2018). Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis. Nature, 560, 192-197.
- Thomas MG, De Rycker M, et al….Read KD and Miles TJ (2019). Identification of GSK3186899/DDD853651 as a Preclinical Development Candidate for the Treatment of Visceral Leishmaniasis. J. Med. Chem., 62, 1180-1202
- Wyllie S, Brand S, Thomas M, et al……Gilbert IH, Read KD, Marco M and Wyatt PG (2019). Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition. PNAS, 116, 9318-9325.
- Thomas M, Brand S, De Rycker M, Zuccotto F, Lukac I, Dodd PG, 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 JM, Martin J, Wyatt PG, Miles TJ, Read KD, Marco M and Gilbert IH (2021). Scaffold-Hopping Strategy on a Series of Proteasome Inhibitors Led to a Preclinical Candidate for the Treatment of Visceral Leishmaniasis. J. Med. Chem., 64, 5905-5930.
I continue to be involved in a large number of diverse small molecule drug discovery programmes, many of which are ongoing or unpublished.
Innovation is also a key passion of mine as evidenced being a key player in redefining the CNS drug discovery lead optimisation process:
- 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
I have a number of investigative projects currently ongoing that could have significant impact on the drug discovery pathway for the diseases that we focus on or more broadly.
I have over 32 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. As a DMPK leader, with particular expertise in CNS and anti-infective drug discovery, I have achieved a considerable track record of success, playing a significant part in 11 compounds entering pre-clinical development, 8 of which have entered clinical trials.
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 build a DMPK group from the ground up. I now have a team of 20 DMPK scientists with extensive Biopharma DMPK experience. I have also led the development within the DDU of key rodent models of disease for the kinetoplastid diseases; Human African trypanosomiasis, Visceral Leishmaniasis and Chagas’ disease. My group has all the skills and tools necessary to ensure that only those molecules with appropriate developability to deliver the required target product profile will progress toward candidate nomination.
I have also been on the DDU management team since joining the DDU in 2008 and I am also on the board for our Wellcome Centre that was awarded in 2017. I have helped grow the DDU to over 130 scientists delivering a fully integrated drug discovery engine embedded in Academia. I have brought in, and continue to bring in, substantial funding to the DDU from sources such as Wellcome and the Bill and Melinda Gates Foundation and currently I am a lead investigator on active grants with income >£16M/ year. I have strong fully integrated collaborations with a number of major Pharma companies.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
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Development of LRRK2 Type II Inhibitors to Understand Utility of these Compounds for the Treatment of Parkinson's Disease
Alessi, D., Davies, P., Gilbert, I., Gray, D. & Read, K.
1/01/23 → 31/12/23
MRC IAA 2021 University of Dundee
Ferguson, M., Gilbert, I., Gray, D. & Read, K.
1/04/22 → 31/03/25
Development Of A Drug Discovery Platform Targeting Salmonella Typhimurium PersisterCells
Bergkessel, M., Coulthurst, S., Gilbert, I. & Read, K.
14/10/21 → 13/10/23
Refining the Drug Discovery Paradigm for Schistosomiasis (Joint with the Universities of Aberystwyth & Cardiff)
Gilbert, I., Gray, D., Read, K. & Wyatt, P.
1/10/21 → 1/04/24
Anti-trypanosomatid drug discovery: progress and challengesDe Rycker, M., Wyllie, S., Horn, D., Read, K. D. & Gilbert, I. H., 31 Jan 2023, In: Nature Reviews Microbiology. 21, p. 35-50 16 p.
Research output: Contribution to journal › Review article › peer-reviewOpen AccessFile
Compounds enhancing human sperm motility identified using a high-throughput phenotypic screening platformGruber, F. S., Johnston, Z. C., Norcross, N. R., Georgiou, I., Wilson, C., Read, K. D., Gilbert, I. H., Swedlow, J. R., Martins da Silva, S. & Barratt, C. L. R., Mar 2022, In: Human Reproduction. 37, 3, p. 466-475 10 p.
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile56 Downloads (Pure)
Drug discovery research in Ghana, challenges, current efforts, and the way forwardAmewu, R. K., Amoateng, P., Arthur, P. K., Asare, P., Asiamah, I., Boamah, D., Darko Otchere, I., Dzidzor Amengor, C., Ekuadzi, E., Chibale, K., Farrell, S. J., Appiah-Oppong, R., Osei-Safo, D., David Read, K., Hugh Gilbert, I. & Yeboah-Manu, D., 15 Sept 2022, In: PLoS Neglected Tropical Diseases. 16, 9, 9 p., e0010645.
Research output: Contribution to journal › Review article › peer-reviewOpen AccessFile
Identification and development of a series of disubstituted piperazines for the treatment of Chagas diseaseMcGonagle, K., Tarver, G. J., Cantizani, J., Cotillo, I., Dodd, P. G., Ferguson, L., Gilbert, I. H., Marco, M., Miles, T., Naylor, C., Osuna-Cabello, M., Paterson, C., Read, K. D., Pinto, E. G., Riley, J., Scullion, P., Shishikura, Y., Simeons, F., Stojanovski, L., Svensen, N., & 5 others, 5 Aug 2022, In: European Journal of Medicinal Chemistry. 238, 14 p., 114421.
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile25 Downloads (Pure)
Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugsGreen, S. R., Davis, S. H., Damerow, S., Engelhart, C. A., Mathieson, M., Baragaña, B., Robinson, D. A., Tamjar, J., Dawson, A., Tamaki, F. K., Buchanan, K. I., Post, J., Dowers, K., Shepherd, S. M., Jansen, C., Zuccotto, F., Gilbert, I. H., Epemolu, O., Riley, J., Stojanovski, L., & 25 others, 11 Oct 2022, In: Nature Communications. 13, 12 p., 5992.
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile
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”
Brandon, A. (Creator), Antonides, L. (Creator), Riley, J. (Contributor), Epemolu, O. (Contributor), Read, K. (Creator) & McKenzie, C. (Creator), University of Dundee, Mar 2021
In Conversation With... Ian and Kev: Industry, Academia and Drug Discovery
Ali Floyd (Host), Lauren Webster (Chair), Catharine Goddard (Organiser), Andrew Cairns (Organiser), Kevin Read (Interviewee), Ian Gilbert (Interviewee) & Ailsa Mackintosh (Organiser)27 Jan 2021
Activity: Other activity types › Public engagement and outreach - public lecture/debate/seminar
Dundee Discoveries Past and Present - self-guided walking tours
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
Discovery Days 2019
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
A Forensic Approach to Street Drugs
1 Media contribution
Tuberculosis drug may also target visceral leishmaniasis
1 item of Media coverage
Automated design for Drug Discovery
Andrew L. Hopkins, Suzanne Norval, Jeremy Besnard, Laste Stojanovski, Richard Bickerton, Kevin Read & Ian Gilbert
1 item of Media coverage