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Publications

Below is a list of selected publications from our team.

2022

Virtual screening directly identifies new fragment-sized inhibitors of carboxylesterase Notum with nanomolar activity. Steadman, B. A. Atkinson, Y. Zhao, N. J. Willis, S. Frew, A. Monaghan, C. Patel, E. Armstrong, K. Costelloe, L. Magno, M. Bictash, E. Y. Jones, P. V. Fish, F. Svensson. J. Med. Chem., 2022, 65, 562-578.

2021

Structural Insight into Notum Covalent Inhibition. Zhao, F. Svensson, D. Steadman, S. Frew, A. Monaghan, M. Bictash, T. Moreira, R. Chalk, W. Lu, P. V. Fish. E. Y. Jones. J. Med. Chem., 2021, 64, 11354-11363.

Small molecule inhibitors of carboxylesterase Notum (Special Report). Zhao, S. Jolly, S. Benvegnu, E. Y. Jones, P. V. Fish. Fut. Med. Chem., 2021, 13, 1001-1015.

Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson’s disease at Chr16q11.2 and on the MAPT H1 allele. M. P. M. Soutar et al. bioRxiv. 2021, doi: https://doi.org/10.1101/2020.01.06.896241

Carboxylesterase Notum is a druggable target to modulate Wnt signaling (Perspective). E.D. Bayle, F. Svensson, B. A. Atkinson, D. Steadman, N. J. Willis, H. L. Woodward, P. Whiting, J.-P. Vincent, P. V. Fish. J. Med. Chem., 2021, 64, 4289-4311.

TREM2/PLCg2 signalling in immune cells: function, structural insight, and potential therapeutic modulation. L. Magno, T. D. Bunney, E. Mead, F. Svensson, M. N. Bictash. Mol. Neurodegen., 2021, 16:22.

PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages. J. Obst, H. L. Hall-Roberts, T. B. Smith, M. Kreuzer, L. Magno, E. Di Daniel, J. B. Davis, E. Mead. Sci Rep., 2021, 11, 19842.

Enhanced insulin signalling ameliorates C9orf72 hexanucleotide repeat expansion toxicity in Drosophila. M. L. Atilano et al. Elife, 2021, 10:e58565.

NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. D. J. Flanagan et al. Nature, 2021, 594, 430-435.

2020

5-Phenyl-1,3,4-oxadiazol-2(3H)-ones are potent inhibitors of Notum carboxylesterase activity identified by the optimization of a crystallographic fragment screening hit. Mahy, N. J. Willis, Y. Zhao, H. Woodward, F. Svensson, J. Sipthorp, L. Vecchia, R. R. Ruza, J. Hillier, S. Kjaer, S. Frew, A. Monaghan, M. Bictash, P. Salinas, P. Whiting, J.-P. Vincent, E. Y. Jones, P. V. Fish. J. Med. Chem., 2020, 63(21), 12942-12956.

Dysregulated Wnt Signalling in the Alzheimer's Brain. N. D. Aghaizu, H. Jin, P. J. Whiting. Brain Sci., 2020, 10, 902-935

Screening of a custom-designed acid fragment library identifies 1-phenylpyrroles and 1-phenylpyrrolidines as inhibitors of Notum carboxylesterase activity. W. Mahy, M. Patel, D. Steadman, H. L. Woodward, B. N. Atkinson, F. Svensson, N. J. Willis, A. Flint, D. Papatheodorou, Y. Zhao, L. Vecchia, R. R. Ruza, J. Hillier, S. Frew, A. Monaghan, A. Costa, M. Bictash, M. Walter, E. Y. Jones, P. V. Fish. J. Med. Chem., 2020, 63, 9464-9483.

Changing the HTS paradigm: AI driven iterative screening for hit finding. G. Dreiman, M. Bictash, P. V. Fish, L. Griffin, F. Svensson. SLAS Discovery: Advancing the Science of Drug Discovery, 2021, 26, 257-262.

Computational Chemistry on a Budget - Supporting Drug Discovery with Limited Resources. H. Willems, S. De Cesco, F. Svensson. J. Med. Chem. (Perspective), 2020, 63, 10158-10169.

Scaffold-hopping identifies furano[2,3-d]pyrimidine amides as potent Notum inhibitors. N. Atkinson, D. Steadman, W. Mahy, Y. Zhao, J. Sipthorp, E. D. Bayle, F. Svensson, G. Papageorgiou, F. Jeganathan, S. Frew, A. Monaghan, M. Bictash, E. Y. Jones, P. V. Fish. Bioorg. Med. Chem Lett., 2020, 30, 126751.

2019

The proteostasis network provides targets for neurodegeneration. T. M. Newton, J. A. Duce, E. D. Bayle. Brit. J. Pharm., 2019, 176, 3508–3514

Alzheimer’s disease Phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph. L. Magno, C. B. Lessard, M. Martins, V. Lang, P. Cruz, Y. T. Asi, M. Katan, J. Bilsland, T. Lashley, P. Chakrabaty, T. E. Golde, P. J. Whiting. Alzheimer’s Research & Therapy, 2019, 11:16.

Tackling gaps in developing life-changing treatments for dementia Alzheimer’s & Dementia. Mauricio et al. Translational Research & Clinical Interventions, 2019, 5, 241-253

Single-cell quantification of mRNA expression in the human brain. S. Jolly, V. Lang, V. H. Koelzer, C. Sala Frigerio,  L. Magno, P. C. Salinas, P. Whiting, E. Palomer. Sci. Rep., 2019, 9, 12353-12360.

New Approaches for the Treatment of Alzheimer’s Disease. P. V. Fish, D. Steadman, E. D. Bayle, P. Whiting. Bioorg. Med. Chem Lett., 2019, 29, 125-133.

2018

Inhibiting p38 MAPK alpha rescues axonal retrograde transport defects in a mouse model of ALS. K. L. Gibbs, B. Kalmar, E. R. Rhymes, A. D. Fellows, M. Ahmed, P. Whiting, C. H. Davies, L. Greensmith, G. Schiavo. Cell Death Dis., 2018, 9:596-603.

2017

Regioselective and enantiospecific synthesis of the HSP co-inducer arimoclomol from chiral glycidyl derivatives. B. N. Atkinson, H. L. Woodward, J. Sipthorp, P. V. Fish, Org. Biomol. Chem., 2017, 15, 9794-9799.