Sygnature Chemical Services is a leading UK-based provider of premium medicinal chemistry, synthetic chemistry, array / focused library and computational chemistry services. Sygnature delivers high value and quality to clients by applying in-house scientific expertise and state-of-the-art technologies to the discovery of novel drug candidates.

Sygnature’s team of industry-experienced chemists offers an exceptional medicinal chemistry-driven approach to undertaking key elements of the drug discovery process, such as hit identification, hit-to-lead and lead optimisation, to afford drug candidates in a time-efficient and cost-effective manner. We work closely with our clients’ scientists to increase the value of their discovery projects and accelerate their compounds into development.

FTE-based medicinal chemistry projects

Sygnature undertakes FTE-based medicinal chemistry projects for clients. Sygnature’s team of 30 chemists (75% PhD qualified) has good experience in drug discovery and the ability to deliver quality compounds to accelerate clients’ discovery programmes.

We contribute resources, chemistry expertise, intellectual input and drug discovery know-how to our collaborations. Sygnature’s multi-national team of scientists has been assembled from leading pharmaceutical and biotechnology companies and drug discovery CROs. They have extensive experience across a range of biological targets (kinases, GPCRs, ion channels, nuclear receptors, proteases, etc.) and therapeutic areas (oncology, inflammation, CNS, metabolic diseases, CV, etc.).

During the course of collaboration, Sygnature’s scientists utilise their understanding of the key factors that influence the outcome of a medicinal chemistry-driven drug discovery, such as computational chemistry data, structure-activity relationships, in vitro and in vivo biological data, drug metabolism, physico-chemical properties, etc. We work closely with clients, focusing on integrated project management and open communication. Our chemists use electronic notebooks, with secure remote access for our clients, to facilitate complete transparency during collaborations.

Virtual screening to deliver lead-like compounds

The application of virtual screening based on protein target structures, homology modelling or ligand structure can deliver enumerated and fully profiled virtual libraries with desirable lead-like properties. Our unique approach to high-throughput chemistry uses reaction scanning, design of experiment software and automated purifications. Arrays of 20-500 compounds can be produced in 1mg-100mg scales with purities >95% by LC-MS.

Hit-to-lead chemistry

The key objectives of the H-2-L phase are, typically, to rapidly confirm that true SAR exists within a number of chemical series and to establish the way forward with potency and selectivity. At Sygnature, we usually make use of parallel chemistry to prepare small arrays with sufficient quantities to allow ADME profiling.

Also, in silico profiling and quick turnaround of biological screening data is important to make progress quickly. This phase usually identifies which liabilities need to be addressed in the lead optimisation (LO) phase.

Lead optimisation to accelerate drug candidates into development

Once a LO programme commences, chemists at Sygnature endeavour to rapidly identify compounds that define and match the target product profile (TPP) and establish ‘proof-of-concept’using in vivo studies. Close cooperation with the client’s scientists is essential to ensure delivery of the candidate in the shortest possible timeframe. Early stage scale-up studies and exemplification for patent purposes also usually take place during this phase. Most importantly, an understanding of the aspects of the molecules that modulate the PK/PD profile must be established in relevant animal models.

Custom synthesis

Sygnature’s chemists have wide-ranging synthetic chemistry expertise and are able to perform multi-stage synthesis, natural product chemistry and chiral synthesis. They can develop synthetic routes to previously unknown compounds, utilise their expertise in flow chemistry and microwave synthesis, and undertake process chemistry. Sygnature operates from milligram to large gram quantities.

Enantioselective synthesis and chiral resolutions

Drug discovery programmes are likely to involve chiral molecules at some stage. Sygnature has considerable expertise in enantioselective synthesis and the resolution of chiral compounds using a variety of techniques; for example, chiral HPLC and classical resolutions.

Chemical optimisation

Reaction or route optimisation approaches are typically applied throughout the discovery process to develop chemical efficiency. Sygnature utilises a range of methods, such as design of experiment (DoE) software, solid supported reagents and scavengers, and flow chemistry, to ensure sufficient materials are synthesised for further evaluation.

About the company

Sygnature has enjoyed healthy growth since its foundation in 2004 because of its ability to deliver flexible resources and drug discovery expertise, but without high overhead costs. During 2008, Sygnature invested £1 million ($1.6 million) to construct modern, purpose-built chemistry laboratories and offices in BioCity Nottingham’s Laurus Building. Sygnature currently employs 40 staff and has clients in the US, UK and Europe. The company’s ethos of value creation for clients, coupled with close working relationships and complete transparency, has been the key to our success.