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Address: BioCity, Pennyfoot Street Nottingham, NG1 1GF
Tel: +44 115 941 5401
Sygnature Discovery is the United Kingdom’s largest independent provider of integrated drug discovery resource and expertise. Founded in 2004, the company undertakes target validation, hit identification, hit-to-lead and lead optimisation projects, and complete drug discovery programmes for pharmaceutical companies. Core capabilities include medicinal chemistry, in vitro bioscience, computational sciences and informatics, DMPK/physical sciences and protein crystallography. Sygnature has an enviable track record of success for delivering multiple drug candidates on client projects.
Sygnature’s integrated drug discovery experience encompasses:
- In vitro validation of novel disease modifying targets in multiple protein classes and across numerous therapeutic areas.
- Experience in tailored assay development to employ a multi-validation approach to understand the presumed role of the biological target.
- Virtual high-throughput Screening (vHTS)
- Protein Production
- High-throughput Screening (HTS)
- Fragment-based Screening
- Medicinal Chemistry
- Knowledge-based Design
- Projects typically run for 6 – 9 months and 2 to 3 lead series are usually selected for progression into lead optimisation.
- Rapidly confirm that a true structure-activity relationship (SAR) exists within a number of hit series for the biological target.
- Start to improve key physico-chemical properties, such as metabolic stability, and establish the way forward with improving potency and selectivity of compounds for the target.
- In silica profiling of compounds used by medicinal chemists to focus synthetic strategies and scaffold core-hopping techniques used to generate new hit series with improved properties.
- Projects typically run for 12 – 18 months to afford a development candidate and a back-up.
- Co-location of Sygnature’s drug discovery departments facilitates an efficient design, make, test, analyse cycle to accelerate project advancement.
- In vivo pharmacokinetic (PK) and pharmacodynamics (PD) ‘proof-of-concept’ data obtained from relevant disease models provides invaluable information to guide project progression.
- Scale-up drug candidates (up to 0.5Kg) for early non-GLP pre-clinical development.
- Scientists frequently named as inventors on clients’ patents.
Integrated Drug Discovery
- Intelligent integrated drug discovery delivers small molecules for advancement from the discovery phase into pre-clinical development and into the clinic.
- Co-location of medicinal chemistry, in vitro bioscience, computational sciences and informatics, and DMPK/physical sciences offers an efficient design, make, test, analyse cycle to fast-track project advancement.
- Key area of expertise include oncology, respiratory, metabolic disease and CNS disorders.
- Unique and synergistic combination of in-house resource and expertise, and a federation of centres of drug discovery excellence located around the world.
Fragment-based Drug Discovery
- FBDD offers an attractive alternative to HTS as only several hundred molecular fragments are screened, rather than many thousands of compounds tested during HTS.
- Sygnature has designed and synthesised a unique, proprietary fragment-based library to aid clients in their drug discovery activities.
- Fragments tend to display a much lower affinity to their target protein versus classic hit-like or lead-like compounds, hence screening is carried-out at elevated concentrations using techniques such as SPR, DSF, NMR and X-ray crystallography.
Sygnature’s core capabilities include:
- One of the largest, most experienced and best equipped medicinal chemistry departments in the UK.
- International team of pharmaceutical industry-experienced medicinal chemists (80% PhD qualified).
- Consistently created value for clients and delivered results which have accelerated drug discovery projects into pre-clinical development.
- FTE-based collaborations are regularly renewed and expanded, amply demonstrating our clients’ confidence in our ability to deliver pivotal results.
- Considerable drug discovery experience with small molecules and biologicals across a broad range of therapeutic areas and biological target classes (>80% PhD qualified).
- Expert at establishing and performing biochemical, cellular and biophysical assays utilising industry-standard screening technologies.
- Knowledge and expertise to design and develop tailored assays and build complete in vitro and in vivo, disease-specific and target-selective screening cascades.
- Incorporate novel techniques, such as biophysics (SPR and DSF) and live cell imaging (IncuCyte ZOOM and ImageXpress) into screening cascades to produce pivotal data.
Computational Sciences and Informatics
- Computational scientists (86% PhD qualified) support drug discovery projects during target analysis, hit identification, hit-to-lead and lead optimisation.
- Virtual high-throughput screening (vHTS) of ~8 million compounds to identify synthetically-tractable small molecules during hit identification projects.
- Robust and cutting-edge informatics infrastructure which allows clients from anywhere in the world to keep up-to-date with projects.
- Electronic laboratory note books with secure remote access for clients; documents and data securely stores and shared via Dotmatics database.
- All Sygnature scientists have on-line access to a wide range of scientific journals. Also specialist patent searching capability and pharmaceutical intelligence.
DMPK and Physical Sciences
- Dedicated to the understanding of the absorption, distribution, metabolism and excretion of drug candidates.
- Our scientists not only undertake a range of industry-standard in vitro DMPK assays, but also have the expertise to interpret the data generated and make project recommendations.
- Know-how and experience to provide a comprehensive consultancy service to interpret in vitro DMPK and in vivo PK / PD data generated elsewhere.
- Peak Proteins Limited, an affiliate company, undertakes construct design, protein expression and protein purification of the required protein.
- Proteins can be supplied in formats suitable for in vitro assays, HTS, biophysics assays, in vivo studies or X-ray crystallography.
- Proteins may be expressed in E.coli, baculovirus/insect cells and mammalian cells, as appropriate.
- Full range of X-ray capabilities from sparse matrix crystallisation screens to 3D structural representations.