Our laboratory focuses on chemical biology approaches at a basic research level to identify and understand new biological mechanisms. We also concentrate on harnessing medicinal chemistry methods to target biological processes with the aim to develop new small molecules therapeutics.

We have strong collaborations with researchers both within our institute and externally, across a variety of disciplines, including:
– high throughput screening
– structural biology
– parasitology
– oncology

Our team works closely with industry partners in several drug discovery programs dedicated to developing new therapeutics in the cancer and infectious disease fields.

Our laboratory has interests in:
– Design of small molecule inhibitors of aspartyl proteases to understand their role in the malaria and cryptosporidiosis.
– Design of small molecules to target SH2 domain proteins to investigate their role in inflammation and cancer.
– Identification of the mechanism of action of small molecule antimalarials currently under optimisation in our laboratory.
– Development of small molecule therapies to treat human and animal helminthiasis.


Selected publications from Dr Brad Sleebs

1. Ashton, T. D.; Dans, M.G.; Favuzza, P.; Ngo, A.; Lehane, A. M.; Zhang, X.; Qiu, D.; Chandra Maity, B.; De, N.; Schindler, K.A.; Yeo, T.; Park, H.; Uhleman, A.-C.; Churchyard, A.; Baum, J.; Fidock, D.A.; Jarman, K.E.; Lowes, K. N.; Baud, D.; Brand, S.; Jackson, P. F.; Cowman, A. F.; Sleebs, B. E. Optimization of 2,3-dihydroquinazoline-3-carboxamides as antimalarials targeting PfATP4. J. Med. Chem. 2023, PMID: 36812492

2. Nguyen, W.; Dans, M. G.; Currie, I.; Awalt, J. K.; Bailey, B. L.; Lumb, C.; Ngo, A.; Favuzza, P.; Palandri, J.; Ramesh, S.; Penington, J. S.; Jarman, K. E.; Mukherjee, P.; Chakraborty, A.; Maier, A. G.; van Dooren, G. G.; Papenfuss, T.; Wittlin, S.; Churchyard, A.; Baum, J.; Winzeler, E.A.; Baud, D.; Brand, S.; Jackson, P. F.; Cowman, A. F.; Sleebs, B. E.7- N-Substituted-3-oxadiazole Quinolones with Potent Antimalarial Activity Target the Cytochrome bc1 Complex. ACS Infect. Dis. 2023, PMID: 36853190

3. Chen H.; Nguyen, N.; Magtoto, C; Cobbold, S.; Richardson, L. W.; Meza, L.; Au, A.; Corbin, J.; Lechtenberg, B.; Sutherland, K.; Feltham, B.; Grohmann, C.; Nicholson, S. N.; Sleebs, B. E. Design and characterization of a heterobifunctional degrader of KEAP1. Redox. Biol. 2023, 59, 102552. PMID: 36473314

4. Chen H.; Li, K.; Wu, Y.; Currie, I.; Keating, N.; Dehkhoda, F.; Grohmann, C.; Babon, J. J.; Nicholson, S. N.; Sleebs, B. E. Optimization of phosphotyrosine peptides that bind to the SH2 domain of SOCS1 and block substrate ubiquitination. ACS Chem. Biol. 2022, 17(2), 449–462. PMID: 34989544

5. Nguyen, W.; Dans, M. G.; Ngo, A.; Gancheva, M. R.; Romeo, O.; Duffy, S.; de Koning-Ward, T. F.; Lowes, K. N.; Jousset Sabroux, H.; Avery, V. M.; Wilson, D. W.; Gilson, P.R.; Sleebs, B.E. Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion. Eur. J. Med. Chem. 2021, 214, 113253. PMID: 33610028

6. Nguyen, W.; Lee, E. F.; Evangelista, M.; Lee, M.; Harris, T. J.; Colman, P. M.; Williams, L. B.; Smith, N.; Lowes, K. N.; Haeberli, C.; Keiser, J.; Smith, B. J.; Fairlie, D. W. Sleebs, B. E. Optimization of benzothiazole and thiazole hydrazones as inhibitors of schistosome BCL-2. ACS Infect. Dis. 2021, 7(5) 1143-1163. PMID: 33523649

7. Currie, I.; Sleebs, B. E. Synthesis of acyl phosphoramidates via a modified Staudinger reaction. Org. Lett. 2021, 23(2) 464-468. PMID: 33379864

8. Chen H.; Mao R.; Brzozowski, M; Nguyen, N.; Sleebs, B. E. Late stage phosphotyrosine mimetic functionalization of peptides employing a nickel-catalyzed photoredox cross-coupling. Org. Lett. 2021, 23, 11, 4244-4249. PMID: 34029466

9. Bailey, B. L.; Nguyen, W.; Ngo, A.; Goodman, C. D.; Gancheva, M. R.; Favuzza, P.; Sanz, L. M.; Gamo, F-J.; Lowes, K. N.; McFadden, G. I.; Wilson, D. W.; Laleu, B.; Brand S.; Jackson, P. F.; Cowman, A. F.; Sleebs, B. E. Optimization of 2-(N-phenyl carboxamide) triazolopyrimidine antimalarials with moderate to slow acting erythrocytic stage activity. Bioorg. Chem. 2021, 115, 105244. PMID: 34452759

10. Nguyen, W.; Jacobson, J.; Jarman, K. E.; Blackmore, T. R.; Jousset Sabroux, H.; Lewin, S. R.; Purcell, D. F.; Sleebs, B. E. Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazolopyridines as potential HIV-1 latency reversing agents. Eur. J. Med. Chem. 2020, 195, 112254. PMID: 32109369

Lab research projects

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