Members

University of Dundee

DDU Website

Drug Discovery Unit

Dundee, Scotland

Member since 2013

Representative

Laura Cleghorn, Ph.D. Tuberculosis Portfolio Manager

Team

  • Simon Green
  • Kevin Read
  • Colin Robinson

About

The Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research is a fully integrated, “Biotech-style” drug discovery operation of 130 scientists, with a remit to complement Biotech/Pharma activities by tackling early-stage small molecule drug discovery across a range of therapeutic areas. We have a remit to address unmet medical need for infectious diseases of low- and middle-income countries, including TB, leishmaniasis, Chagas disease, cryptosporidiosis, schistosomiasis and malaria. Our projects and skillsets cover all aspects of early drug discovery, from hit identification, through lead optimisation to candidate selection. Our experienced team, many of whom have a background in Biotech/Pharma, works in a state-of-the-art building with cutting-edge equipment and automation for drug discovery.

Role & Expertise

Our Gates Foundation funded TB drug discovery activities, focus on identifying safe and orally dosed candidates with the greatest potential to contribute to drug regimens that will significantly reduce the duration of TB drug therapy. We work on assets arising from phenotypic screening and target-based projects, focusing on computational and medicinal chemistry, DMPK and target assays; relying on members of the TBDA to carry out all TB biology, from primary screening, mode of action determination to in vivo testing. The DDU works with the NIAID, on a high throughput in vitro method to determine the rate and routes of compound metabolism by TB.

Links

Tale a virtual tour

Drug Discovery Unit

References

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  6. Oh, S.; Libardo, M. D. J.; Azeeza, S.; Pauly, G. T.; Roma, J. S. O.; Sajid, A.; Tateishi, Y.; Duncombe, C.; Goodwin, M.; Ioerger, T. R.; Wyatt, P. G.; Ray, P. C.; Gray, D. W.; Boshoff, H. I. M.; Barry, C. E. Structure–Activity Relationships of Pyrazolo[1,5- a ]Pyrimidin-7(4 H )-Ones as Antitubercular Agents. ACS Infectious Diseases2021, 7 (2), 479–492. https://doi.org/10.1021/acsinfecdis.0c00851.
  7. Soares De Melo, C.; Singh, V.; Myrick, A.; Simelane, S. B.; Taylor, D.; Brunschwig, C.; Lawrence, N.; Schnappinger, D.; Engelhart, C. A.; Kumar, A.; Parish, T.; Su, Q.; Myers, T. G.; Boshoff, H. I. M.; Barry, C. E.; Sirgel, F. A.; Van Helden, P. D.; Buchanan, K. I.; Bayliss, T.; Green, S. R.; Ray, P. C.; Wyatt, P. G.; Basarab, G. S.; Eyermann, C. J.; Chibale, K.; Ghorpade, S. R. Antitubercular 2-Pyrazolylpyrimidinones: Structure-Activity Relationship and Mode-of-Action Studies. Journal of Medicinal Chemistry 2021, 64 (1), 719–740. https://doi.org/10.1021/ACS.JMEDCHEM.0C01727.
  8. Wang, Q.; Boshoff, H. I. M.; Harrison, J. R.; Ray, P. C.; Green, S. R.; Wyatt, P. G.; Barry, C. E. PE/PPE Proteins Mediate Nutrient Transport across the Outer Membrane of Mycobacterium Tuberculosis. Science 2020, 367 (6482). https://doi.org/10.1126/science.aav5912.
  9. Cleghorn, L. A. T.; Ray, P. C.; Odingo, J.; Kumar, A.; Wescott, H.; Korkegian, A.; Masquelin, T.; Lopez Moure, A.; Wilson, C.; Davis, S.; Huggett, M.; Turner, P.; Smith, A.; Epemolu, O.; Zuccotto, F.; Riley, J.; Scullion, P.; Shishikura, Y.; Ferguson, L.; Rullas, J.; Guijarro, L.; Read, K. D.; Green, S. R.; Hipskind, P.; Parish, T.; Wyatt, P. G. Identification of Morpholino Thiophenes as Novel Mycobacterium Tuberculosis Inhibitors, Targeting QcrB. Journal of Medicinal Chemistry 2018, 61 (15), 6592–6608. https://doi.org/10.1021/ACS.JMEDCHEM.8B00172.
  10. Homeyer, N.; van Deursen, R.; Ochoa-Montaño, B.; Heikamp, K.; Ray, P.; Zuccotto, F.; Blundell, T. L.; Gilbert, I. H. A Platform for Target Prediction of Phenotypic Screening Hit Molecules. Journal of Molecular Graphics and Modelling 2020, 95, 107485. https://doi.org/10.1016/j.jmgm.2019.107485.
  11. Park, Y.; Ahn, Y.-M.; Jonnala, S.; Oh, S.; Fisher, J. M.; Goodwin, M. B.; Ioerger, T. R.; Via, L. E.; Bayliss, T.; Green, S. R.; Ray, P. C.; Wyatt, P. G.; Barry, C. E.; Boshoff, H. I. Inhibition of CorA-Dependent Magnesium Homeostasis Is Cidal in Mycobacterium Tuberculosis. Antimicrobial Agents and Chemotherapy 2019, 63 (10). https://doi.org/10.1128/AAC.01006-19.
  12. Smith, P. W.; Zuccotto, F.; Bates, R. H.; Martinez-Martinez, M. S.; Read, K. D.; Peet, C.; Epemolu, O. Pharmacokinetics of β-Lactam Antibiotics: Clues from the Past To Help Discover Long-Acting Oral Drugs in the Future. ACS Infectious Diseases2018, 4 (10), 1439–1447. https://doi.org/10.1021/acsinfecdis.8b00160.
  13. Prati, F.; Zuccotto, F.; Fletcher, D.; Convery, M. A.; Fernandez-Menendez, R.; Bates, R.; Encinas, L.; Zeng, J.; Chung, C.; De Dios Anton, P.; Mendoza-Losana, A.; Mackenzie, C.; Green, S. R.; Huggett, M.; Barros, D.; Wyatt, P. G.; Ray, P. C. Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium Tuberculosis InhA. ChemMedChem 2018, 13 (7), 672–677. https://doi.org/10.1002/cmdc.201700774.
  14. Murugesan, D.; Ray, P. C.; Bayliss, T.; Prosser, G. A.; Harrison, J. R.; Green, K.; Soares de Melo, C.; Feng, T.-S.; Street, L. J.; Chibale, K.; Warner, D. F.; Mizrahi, V.; Epemolu, O.; Scullion, P.; Ellis, L.; Riley, J.; Shishikura, Y.; Ferguson, L.; Osuna-Cabello, M.; Read, K. D.; Green, S. R.; Lamprecht, D. A.; Finin, P. M.; Steyn, A. J. C.; Ioerger, T. R.; Sacchettini, J.; Rhee, K. Y.; Arora, K.; Barry, C. E.; Wyatt, P. G.; Boshoff, H. I. M. 2-Mercapto-Quinazolinones as Inhibitors of Type II NADH Dehydrogenase and Mycobacterium Tuberculosis : Structure–Activity Relationships, Mechanism of Action and Absorption, Distribution, Metabolism, and Excretion Characterization. ACS Infectious Diseases 2018, 4 (6), 954–969. https://doi.org/10.1021/acsinfecdis.7b00275.
  15. Park, Y.; Pacitto, A.; Bayliss, T.; Cleghorn, L. A. T.; Wang, Z.; Hartman, T.; Arora, K.; Ioerger, T. R.; Sacchettini, J.; Rizzi, M.; Donini, S.; Blundell, T. L.; Ascher, D. B.; Rhee, K.; Breda, A.; Zhou, N.; Dartois, V.; Jonnala, S. R.; Via, L. E.; Mizrahi, V.; Epemolu, O.; Stojanovski, L.; Simeons, F.; Osuna-Cabello, M.; Ellis, L.; MacKenzie, C. J.; Smith, A. R. C.; Davis, S. H.; Murugesan, D.; Buchanan, K. I.; Turner, P. A.; Huggett, M.; Zuccotto, F.; Rebollo-Lopez, M. J.; Lafuente-Monasterio, M. J.; Sanz, O.; Diaz, G. S.; Lelièvre, J.; Ballell, L.; Selenski, C.; Axtman, M.; Ghidelli-Disse, S.; Pflaumer, H.; Bösche, M.; Drewes, G.; Freiberg, G. M.; Kurnick, M. D.; Srikumaran, M.; Kempf, D. J.; Green, S. R.; Ray, P. C.; Read, K.; Wyatt, P.; Barry, C. E.; Boshoff, H. I. Essential but Not Vulnerable: Indazole Sulfonamides Targeting Inosine Monophosphate Dehydrogenase as Potential Leads against Mycobacterium Tuberculosis. ACS Infectious Diseases 2017, 3 (1), 18–33. https://doi.org/10.1021/acsinfecdis.6b00103.
  16. Sarathy, J. P.; Zuccotto, F.; Hsinpin, H.; Sandberg, L.; Via, L. E.; Marriner, G. A.; Masquelin, T.; Wyatt, P.; Ray, P.; Dartois, V. Prediction of Drug Penetration in Tuberculosis Lesions. ACS Infectious Diseases 2016, 2 (8), 552–563. https://doi.org/10.1021/acsinfecdis.6b00051.
  17. Arora, K.; Ochoa-Montaño, B.; Tsang, P. S.; Blundell, T. L.; Dawes, S. S.; Mizrahi, V.; Bayliss, T.; Mackenzie, C. J.; Cleghorn, L. A. T.; Ray, P. C.; Wyatt, P. G.; Uh, E.; Lee, J.; Barry, C. E.; Boshoff, H. I. Respiratory Flexibility in Response to Inhibition of Cytochrome c Oxidase in Mycobacterium Tuberculosis. Antimicrobial Agents and Chemotherapy 2014, 58 (11), 6962–6965. https://doi.org/10.1128/AAC.03486-14.

More

The WCAIR Training Programme aims to support individuals from low-middle income countries working in drug discovery. We provide a range of training options, from short courses (both online and face-to-face), funded training placements in Dundee, to bespoke support for institutions to help develop their skills in drug discovery research. Our training placements in Dundee are designed to support the individual researcher, building upon the skills they have and allowing them to learn new skills and techniques that can be transferred to their own institution. Our team of trainers work with the experts in WCAIR to ensure that individuals gain as much experience as possible during their placement. Where possible, trainees are placed into working drug discovery portfolios to see how the scientists interact in a live project.

We run a number of short courses, some that cover all aspects of running a drug discovery programmes, while others are designed to teach very specific skills or techniques. We work with a number of institutions in different countries to support their own requirements, developing programmes which are suitable for their researchers. We have also developed some online resources which are free to access https://wcair.dundee.ac.uk/training/training-resources/.

For further details please see https://wcair.dundee.ac.uk/training/ or contact the training manager Suze Farrell at [email protected]