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Identification of novel diverse hit compounds via high-throughput virtual screening

Country of Origin: United Kingdom
Reference Number: TOUK20170607001
Publication Date: 5 July 2019

Summary

An East of England startup offers service agreements to small pharma companies, to do high-throughput virtual screening. The diverse library gets screened against a large number of known proteins, to predict biological activity and off target effects where possible. At the same time, academia and biotech companies are invited to add their targets or compounds to the body of knowledge under a license agreement.

Description

A spinout from the chemistry department of a renowned University in the East of England is launching a most advanced tool for generating drug hits.



The drug discovery process can start with a screen, to see which chemical compounds bind to proteins that are known to be involved in disease processes. Such binding molecules are called ligands and the respective proteins targets. The binding molecules seldom make it all the way to become a drug. This initial ‘hit’ will provide valuable clues with regards to how easily the protein can be targeted. There is a long way to go still, as these hits may bind to a number of proteins in the body. During an optimization process, the molecules get tailored so as to become ever more specific towards the target, whilst showing less and less binding to all the other proteins. This unwanted binding may be outright toxic or interfere with the desirable effect of the target protein, the therapeutic effect. To make it more complex, a good drug candidate must be good with regards to membrane transport and various other body functions to ensure that it stays in the body for a feasible amount of time, does its job, and then gets excreted.



The problems with the pharmaceutical development funnel are well-known. The sheer complexity of therapeutic pathways pushes many promising drug candidates over the edge. They interfere where they shouldn’t interfere.



This new spinout has been amassing knowledge in two aspects relating to this problem. On the one hand, they have built proprietary capabilities in computational and medicinal chemistry, to handle this growing complexity. On the other, they have compiled world-leading diverse database of small molecules.



The result is this: a partner comes in with a target protein, wishing to generate hits with high potency. The algorithm runs the virtual candidates against thousands of protein structures with known ligands. It is important to stress the objectives with the virtual compound library are; 1) the chemical diversity is the broadest the company is aware of, and, 2) the synthetic access has been built in, meaning that over 95% of the virtual results can actually be synthesised.



So, the binding scores will be returned for both the target and the thousands of known proteins, involved in cytotoxicity, membrane transport, and many other aspects. The 10 most potent hits have different profiles in terms of selectivity and cytotoxicity. Dependent on the discovery programme, such cross-binding is either unwanted (for maximum selectivity) or wanted (for polypharmacology). 



Such a virtual programme is much faster, and cheaper, than a conventional high-throughput screening programme. Also, the company will set out to demonstrate that the probability of generating validated hits is much higher.



The UK company is seeking two types of partners. Firstly, the described programme is being offered to pharma companies under a service agreement. Secondly, enquiries are welcome from academia and biotechnology companies who wish to deposit their structures from either the protein or compound side. In a future event where these turn useful as candidates for new programmes, milestones and in time royalties will be paid under a license agreement.

Advantages and Innovations

This ultra high throughput virtual screening is the most likely way to produce drug candidates for highest possible success in downstream in vivo studies. Much of the desired activity and potential serious off-target activity, has been predicted before any stop/go decision.

Stage Of Development

Available for demonstration

Requested partner

- Type of partner sought: industry and academia. 

- Specific area of activity of the partner: drug discovery. 

- Task to be performed by the partner sought: under a service agreement, the UK company would need to know the structure and the binding site of the target protein. Under a license agreement, the UK company would collect data on new targets and compounds and include them in their body of knowledge.