Driving drug discovery

Sygnature Discovery boosts high-throughput screening capabilities

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NOTTINGHAM, U.K.—Sygnature Discovery, an independent integrated drug discovery and preclinical services company, has added in-house high-throughput screening (HTS) to its range of drug discovery services. The company’s new Leadfinder compound library backs up the process.
HTS enables the testing of many thousands of molecules for activity in a short period of time. Researchers use it for rapid identification of starting points for drug discovery programs.
Sygnature’s new HTS system combines Titian Mosaic sample management technology with an automation platform from HiRes Biosolutions. Genedata software facilitates data analysis. This is the first time these three leading vendors have worked together on the same system to create a high level of data fidelity during the screening operations.
Underpinning the screening capability is the Leadfinder library of 150,000 molecules. Sygnature’s team of computational and medicinal chemists selected the molecules. A further 100,000 compounds will be designed and synthesized in the next five years. The library compounds are kept under dry, cool conditions and in an atmosphere of nitrogen to reduce the likelihood that they will oxidize or decompose in storage.
According to John Unitt, director of bioscience at Sygnature Discovery, “The molecules were all selected to have lead-like molecular properties, and contain no undesirable functional groups. Many commercial chemical libraries contain some molecules with features we would not want to incorporate into a drug lead. We have designed our Leadfinder library to avoid these problems.”
“We decided to build our own HTS capability after feedback from our clients, especially around compound quality in many historical screening libraries,” said Colin Sambrook Smith, Sygnature’s director of computational sciences and informatics. “Having the capability housed within our Nottingham labs, where it can be integrated with our other hit-finding functions, will bring an enormous amount of additional value to our clients and their drug discovery projects.”
Private equity-backed since 2017, the company operates fully enabled research facilities in Nottingham and Alderley Park in the United Kingdom, housing more than 250 research scientists, and also has an office presence in Cambridge, Mass. Experienced drug hunters undertake demanding research programs and drive them from target validation through hit identification, hit-to-lead and lead optimization, to preclinical development candidate. Since 2011, 30 compounds discovered by Sygnature for clients have entered preclinical development. Thus far, 14 of these have progressed to clinical trials (Phases 1, 2 and 3). In 2017, Sygnature Discovery received the Queen’s Award for Enterprise for International Trade.
Since 2004, Sygnature Discovery has offered drug discovery services and provided guidance and support to clients for the discovery and development of novel medicines. It has grown into a multi-award-winning company with a global presence.
According to Dr. Simon Hirst, Sygnature’s CEO, “Having worked in big and medium-sized pharma, I had been involved in outsourcing a number of services and found it a pretty unsatisfactory experience. We often discovered that companies didn’t have the skills to do what we wanted to do. They were not set up the right way, nor did they invest in having the right facilities, the right research capabilities. Communication was also generally poor. Managing outsourced projects was very difficult, and we didn’t feel in control. I felt this could be done a lot a better.”
He added, “It was clear to us that outsourcing drug discovery was going to grow and be part of the future for this industry. Drug discovery had to continue to be done, and be done well and successfully. Everyone will be a patient one day, and as we get older, the likelihood of needing a treatment increases. The old pharma model was not working, it was too rigid and lacked innovation; outsourcing was the new model, a flexible model that would create efficiencies and support the adoption of innovative new approaches. This flexibility just could not happen in big pharma companies.”
A drug discovery CRO, Sygnature Chemical Services started as a small chemistry group with computational chemistry support. The intention was to create an integrated discovery service offering.
Hirst concluded, “Our vision remains for drug discovery to be done better. We believe in doing things differently, to invent and implement new effective processes and pathways that will improve the chances of successful project outcomes.“

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