Structural biology is a key element of many drug discovery projects, providing insights into the binding orientation and conformation of small molecules to their targets. Understanding the binding mode of a small molecule can inform design strategies to increase ligand affinity and reduce design-make-test (DMT) cycle times.
At BioAscent we implement X-ray crystallography studies to drive forward drug discovery projects at all stages including target validation, hit validation and SAR support, and X-ray fragment screening. Our structural biology team have over 30 years’ experience in developing robust crystallography platforms to support drug design projects.
Our scientists place particular emphasis on the development of a fit-for-purpose X-ray crystallography platform for your specific project. Drawing upon our deep knowledge of structural biology techniques, we work closely with you to choose the right approach for your project and maximise the chances of success. Workflows are carefully tailored and executed to ensure that experimental throughput matches discovery timelines and aligns with DMT cycles.
Through our access arrangement with the Diamond Light Source synchrotron (UK) we can measure high-resolution datasets suitable to support structure-based design projects. Our expert crystallographers are experienced in processing, analysing and refining this data, and can assist in the understanding and interpretation of the results.
A consistent supply of high-quality protein is crucial to the success of any structural biology project. BioAscent’s comprehensive protein production capabilities and meticulous quality control ensure access to the highest-quality proteins for your project.
Our computational chemistry team apply a variety of structure-based methodologies to design, assess and optimise ligands, helping you to select the right compounds and set your project up for success.
The discovery of new inhibitors of insulin-regulated aminopeptidase by a high-throughput screening of 400,000 drug-like compounds. J. Gising, S. Honarnejad, M. Bras, G.L. Baillie, S.P. McElroy, P. S. Jones, A. Morrison, J. Beveridge, M. Hallberg, M. Larhed. View paper.
Discovery and characterization of novel TRPML1 agonists. X. Peng, C.J. Holler, A-M.F. Alves, M.G. Oliviera, M. Speake, A. Pugliese, M.R. Oskouei, I.D de Freitas, A.Y.-P. Chen, R. Gallegos, S.M. McTighe, G. Koenig, R.S. Hurst, J-F. Blain, J.C. Lanter, D.A. Burnett. View paper.
Application of particle swarm optimization to understand mechanism of action of allosteric inhibitors of the enzyme HSD14ß13. A. Ford, F. Breitgoff, M. Pasquani, A. MacKenzie, S. McElroy, S. Baker, P. Abrusci, S. Varzandeh, L. Bird, A. Gavard, D. Damerell, M. Redhead. View paper.
The identification and characterisation of autophagy inhibitors from the published kinase inhibitor sets. M. Zachari, J. Rainard, G. Pandarakalam, L. Robinson, J. Gillespie; M. Rajamanickam; V. Hamon; A. Morrison; I. Ganley; S. McElroy. View paper.
Identification of a novel class of benzofuran oxoacetic acid-derived ligands that selectively activate cellular EPAC; Cells; 8(11); 1425; 2019. E. Beck, E. Parnell, A. Cowley, A. Porter J. Gillespie, J. Robinson, L. Robinson A. Pannifer, V. Hamon, P. Jones, A. Morrison, S. McElroy, M. Timmerman, H. Rutjes, P. Mahajan, J. Wiejak, U. Luchowska-Stańska, D. Morgan, G. Barker, H. Rehmann and S. Yarwood. View paper.
Reducing the PAINS in high throughput screening: assay design as a tool for maximising efficiency; Drug Discovery World; Fall 2019, 53. S McElroy, P. Jones. View paper.
Synthesis and structure–activity relationships of N-(4-benzamidino)-oxazolidinones–potent and selective inhibitors of kallikrein-related peptidase 6; chemRxiv DOI: 10.26434/chemrxiv.9788276, 2019. E. De Vita, N. Smits, H. van den Hurk, E. Beck, J. Hewitt, G. Baillie, E. Russell, A. Pannifer, V. Hamon, A.Morrison, S. McElroy, P. Jones, N. Ignatenko, N. Gunkel and A. Miller. View paper.
A high-throughput screen for the identification of compounds that inhibit nematode gene expression by targeting spliced leader trans-splicing. Int J Parasitol Drugs Drug Resist. 2019 Apr 5;10:28-37. doi: 10.1016/j.ijpddr.2019.04.001. G. Pandarakalam, M. Speake, S. McElroy, A. Alturkistani, L. Philippe, J. Pettitt, B. Müller, B. Connolly. View paper.
Targeting Quorum Sensing: High-Throughput Screening to Identify Novel LsrK Inhibitors. Int J Mol Sci. 2019 Jun 25;20(12). pii: E3112. doi: 10.3390/ijms20123112. V. Gatta, P. Ilina, A. Porter, S McElroy, P Tammela. View paper.
Abstract LB-B17: Characterization of small molecule inhibitors of the Nrf2-Keap1 interaction using MicroScale Thermophoresis. Molecular Cancer Therapeutics 17 (1 Supplement), LB-B17-LB-B1. J. Rainard, A. Morrison, A. Pannifer, P. Jones, R. Mead, S. McElroy. View paper.
Comprehensive Medicinal Chemistry III, Chapter 1.18, 505-519; Eds. S. Chackalamannil, D. Rotella, S. Ward; Oxford: Elsevier; 2017. European Lead Factory; F. Giordanetto, P. Jones, A. Nelson, J. Benningshof, G. Muller, A. Pannifer, S. van Boeckel and D. Tzalis. View paper.
The SULSA Assay Development Fund: accelerating translation of new biology from academia to pharma. Drug Discovery Today, February 2017, Volume 22, Issue 2, Pages 199-203. S. McElroy, P. Jones, V. Barrault. View paper.
In Vitro Assay Development and HTS of Small-Molecule Human ABAD/17beta-HSD10 Inhibitors as Therapeutics in Alzheimer’s Disease. SLAS Discovery, 2017, Volume 22, Issue 6, Pages 676-685. L. Aitken, G. Baillie, A. Pannifer, A. Morrison, P. Jones, T. Smith, S. McElroy, F. Gunn-Moore. View paper.
Identification of a Novel, Small Molecule Partial Agonist for the Cyclic AMP Sensor, EPAC1. Nature Scientific Reports 7, 2017, Article number: 294. E. Parnell, S. McElroy, J. Wiejak, G. Baillie, A. Porter, D. Adams, H. Rehmann, B. Smith & S. Yarwood. View paper.
The importance of triaging in determining the quality of output from high-throughput screening. Future Medicinal Chemistry, 2015, Vol. 7, No. 14, Pages 1847-1852. P. Jones, S. McElroy, A. Morrison, A. Pannifer. View paper.
