Introduction

Our Biosciences team is uniquely experienced in de novo assay development and optimisation of bespoke biochemical, biophysical and cellular assays.

Leveraging our extensive range of equipment, we can rapidly develop sensitive and robust assays for hit identification, mechanistic profiling and to support medicinal chemistry programmes across all major target classes, including more novel and challenging examples.

Our in-depth biochemical and biophysical knowledge allows us to develop a profound understanding of the nature of the interactions and to characterise the target-ligand binding, maximising your probability of success.

Assay development case studies

Since 2013, we have built upon our assay development expertise, and established more than 150 bespoke biochemical, biophysical and cellular assays, supporting medicinal chemistry programmes across all major target classes, including novel and challenging targets.

• KLK6: Synthesis and structure-activity relationship of N-(4-benzamidino)-oxazolidinones-potent and selective inhibitors of kallikrein-related peptidase 6. View case study, view paper.

• EPAC: Identification of a novel class of benzofuran oxocetic acid-derived ligands that selectively activate cellular EPAC. View paper. 

• ABAD: In Vitro Assay Development and HTS of Small-Molecule Human ABAD/17beta-HSD10 Inhibitors as Therapeutics in Alzheimer’s Disease. View paper.

SCREENING TRIAGE CASE STUDIES

As part of our development and validation process for bespoke assays, we have developed a set of compounds known to cause interference in assays, so called PAINS activity, that can cause false positive results during screening (e.g. aggregators, redox cyclers, chelators etc.). We use these compounds during assay development to identify potential liabilities and can then either optimise the assay to minimise these ‘false positive’ effects, or in cases where these effects cannot be eliminated, we can put in place appropriate de-selection assays to quickly triage such compounds. 

• Reducing the PAINS in high throughput screening: assay design as a tool for maximising efficiency. View article

• Using a library of Pan-Assay Interference (PAINS) small molecules to understand and improve HTS outcomes. View poster

Target Class Expertise

Capabilities and Techniques

Our Experts

Publications

• Cell-active small molecule inhibitors validate the SNM1A DNA repair nuclease as a cancer target. M. Bielinski, L. R. Henderson, Y. Yosaatmadja, L. P. Swift, H. T. Baddock, M. J. Bowen, J. Brem, P. S. Jones, S. P. McElroy, A. Morrison, M. Speake, S. van Boeckel, E. van Doornmalen, J. van Groningen, H. van den Hurk, O. Gileadi, J. A. Newman, P. J. McHugh,  C. J. Schofield. 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.

• Using Microscale Thermophoresis to Characterize Hits from High-Throughput Screening: A European Lead Factory Perspective. SLAS DISCOVERY: Advancing Life Sciences R&D, Vol 23, Issue 3, pp. 225 – 241. J. Rainard, G. Pandarakalam, 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.

Posters & case studies

• Using a library of Pan-Assay Interference (PAINS) small molecules to understand and improve HTS outcomes. G. Baillie, A. Morrison, A. Pannifer, S. McElroy. Download PDF.

• The use of Dynamic Mass Redistribution (DMR) in the European Lead Factory (ELF): a case study. G. Baillie, O. Watt, S. McElroy. Download PDF.

• Characterization of small molecule inhibitors of the Nrf2-Keap1 interaction using MicroScale Thermophoresis. J. Rainard, M. Matheson, J. Gemmell, A. Morrison, A. Pannifer, P. Jones, R. Mead, S. McElroy. Download PDF.

• The SULSA Assay Development Fund: a model for widening access to high throughput screening. S. McElroy, D. Barrault, P. Jones. Download PDF.

• The European Lead Factory: A Collaborative Approach to Drug Discovery. ESC Chemistry: F. MacLeod, A. Morrison, E. Beck, P. Jones, J. Hewitt, M. Matheson, J. Schulz, J. Robinson, L. Robinson, J. Gillespie, M. Huggett, M. Rajamanickam; ESC CMC: A. Pannifer, V. Hamon; ESC Biology: S. McElroy, M. Speake, G. Baillie, E. Russell, J. Rainard, A. Porter, G. Pandarakalam, N. Clark, D. Tegazzini. PPSC: H. Rutjes, C.A.A. van Boeckel, N. Smits, E. van Doornmalen, T. W. Lam, M. Bras, C. S. Schofield; J. J. Brem; M. A. McDonough, M. Van der Stelt, F. J. Janssen, P.P. Geurink, H. Ovaa, H. S. Overkleeft, A. C. M. van Esbroeck, M. P. Baggelaar, H. den Dulk. Download PDF.

• Lead generation: discovery of novel KLK6 Inhibitors as novel anti-cancer drugs. E. De Vita, N. Smits, H. van den Hurk, E. M. Beck, J. Hewitt, G. Baillie, E. Russell, A. Pannifer, V. Hamon, A.Morrison, S. P. McElroy, P. Jones, N. A. Ignatenko, N. Gunkel and A. K. Miller. View case study.