ALBORADA Drug Discovery Institute identifies advanced Huntington’s leads using BioAscent’s Compound Cloud library

NEWHOUSE, UK (31 January 2019): BioAscent Discovery Limited’s ( unique on-demand compound library, Compound Cloud, has been used by the ALBORADA Drug Discovery Institute for virtual screening and to progress promising leads against a novel Huntington’s disease target.

The ALBORADA Drug Discovery Institute, established by Alzheimer’s Research UK, is developing new approaches to slow or halt the progress of the diseases that cause dementia. The Institute’s primary focus is to explore mechanisms associated with the misfolded, aggregated proteins which characterise most neurodegenerative diseases.

The Institute has an advanced drug discovery program seeking to develop inhibitors of the PI5P4 kinases. Lead Academic Scientist Professor David Rubinsztein has previously used genetic studies to show that blocking these enzymes upregulates autophagy, a natural cellular protein clearance mechanism which is capable of digesting and removing neurotoxic proteins. In cell models, blocking the activity of the enzymes reduced the effects of Huntington’s disease.

Based on these findings, ALBORADA drug discovery team obtained compounds from a variety of sources in order to prosecute a drug discovery program.  Approaches employed included fragment screening, diversity screening and virtual screening. The virtual screening used BioAscent’s on-demand Compound Cloud service which provided quick access to a library of over 125,000 lead-like and drug-like IP-free compounds.

The institute undertook a Virtual Screening approach to select potential hits from Compound Cloud, downloading the structures of the 31,000 kinase inhibitor subset of the library, and selecting potential hits via a number of computational methods (filtering based on sub-structures, docking approaches using a literature crystal structure and pharmacophore approaches based on known ligands of similar targets). Based on their structures, the resulting compounds were assigned to 960 clusters.

In January 2017 the team ordered 960 compounds (10 x 96 well plates) from Compound Cloud, representing the individual clusters, and used these as part of their target-based screening.  Potential hits were re-ordered for confirmatory studies.

The institute has now identified small molecule inhibitors of the PI5P4 kinases and have shown in a range of cell types, including primary neurons, that these compounds upregulate autophagy. The most advanced hits in this program are based on the initial Compound Cloud hits. These hits have been further optimised into potent and selective PI5P4 kinase inhibitors with properties consistent with those of a drug, including oral bioavailability and brain penetration in rodents. In vivo studies are ongoing to test the effects of these autophagy modulators in animal models of neurodegeneration.

Compound Cloud users can download structures of all 125,000 compounds (or pre-filtered subsets thereof), analyse structures and select only those compounds of interest, and have them delivered as liquid samples in the quantity, format and plate layout of their choosing (including near-assay ready plates).  It represents an extremely cost-effective way of accessing either ready-made or customised libraries in the quantities required for a screening program. BioAscent’s integrated drug discovery team also use the library in the drug discovery programs that it carries out for its customers. 

For more information, about BioAscent’s Compound Cloud library, visit


Editors’ Notes

BioAscent Discovery Ltd.

Founded in 2013, BioAscent is a leading provider of integrated drug discovery services based at the former Organon / Merck Sharpe and Dohme (MSD) R&D site in Newhouse, Scotland. Our drug discovery services include de novo assay development, target analysis and bespoke screening strategies, compound screening, medicinal and synthetic chemistry, computational chemistry and data management. Our team of expert scientists has experience of successfully working from assay development through to preclinical and clinical candidates across all biological target classes and major therapeutic indications. As part of its compound management service, BioAscent currently holds and manages over 1 million compounds for our customers, in both liquid and solid formats. Through the Compound Cloud service, the company provides rapid access to an IP-free library of ~125,000 lead like compounds in screening-ready format.  Since 2013, the BioAscent team has been responsible for:

    >100 biochemical and biophysical assays for drug discovery projects

    >50 hit validation/characterisation projects

    >30 hit-to-lead campaigns

    >80,000 screening plates delivered to our global customers/partners

The ALBORADA Drug Discovery Institute

The ALBORADA Drug Discovery Institute sits within the Cambridge Biomedical Campus, one of the largest concentrations of medical research expertise in the world, and is part of a wider Drug Discovery Alliance, funded by the charity Alzheimer’s Research UK in 2014. The Cambridge Drug Discovery Institute will work alongside Institutes at the University of Oxford and University College London to create one of the largest coordinated efforts to drive academic drug discovery into neurodegenerative diseases.

Our drug discovery expertise will bridge the gap between the deep disease understanding of academia and the drug development capabilities within the pharmaceutical/biotechnology industry and clinical centres of excellence.  We intend to engage closely with our industrial and clinical partners during the discovery process, to ensure successful candidates continue through the drug discovery pipeline.



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