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Inflammation and Immunology

Inflammation is a crucial part of the body’s immune response to injury or insult, but it is often painful, and may cause further damage. In extreme cases, it can be fatal. Inflammatory responses that occur inappropriately or are poorly controlled are a major cause of disease, morbidity and poor quality of life.

A range of debilitating diseases result from chronic inflammatory responses. Many are autoimmune diseases, such as asthma, allergy, rheumatoid arthritis and inflammatory bowel disease. Others are metabolic diseases, including fibrosis and NASH. Numerous key cells and functions behind inflammatory disease overlap with targets for immuno-oncology.

Sygnature Discovery has developed a broad understanding of the inflammatory and immune mechanisms and pathways that underpin many disease pathologies. Our expert scientists are highly skilled in the art of developing meaningful and efficient assay cascades to support clients’ research projects. This, coupled with Sygnature’s experienced medicinal chemists and DMPK, offers a truly integrated drug discovery platform that has delivered numerous clinical assets in diseases such as Asthma, COPD and IBD.

Our bioscience department have significant experience in developing in vitro cell assays to measure a range of inflammation and immunological biomarkers, processes and endpoints. The in-house blood donor panel gives ready access to whole blood, PBMC and isolated key immune and inflammatory cells from healthy donors. We can also access both fresh and cryopreserved whole blood and blood-derived cells from patients through our contacts with local hospitals, universities and specialist suppliers.

We use a wide range of assays to study key inflammatory and immune cell functions, and also develop bespoke assays.

Our experienced bioscience team help clients’ projects progress through proof of concept in vivo studies and into the clinic by providing tailored biomarker solutions and human disease-relevant translational assays.

Inflammation assay platforms

We offer a wide range of inflammation assays, including:

  • Modulation of intracellular signalling events, such as calcium, cAMP and phosphoprotein levels in inflammatory cell systems.
  • Proliferation (IncuCyte), chemotaxis, multiplex cytokine release (Luminex), NETosis (cell imaging), pyroptosis, metabolism (Agilent’s Seahorse), gene expression arrays (qPCR).
  • Differentiation of human naïve cells to produce more disease-relevant cell phenotypes, including M1 and M2 macrophages and neuro-inflammatory microglia cells.
  • Flow cytometry and cell imaging can be used to identify and assess the functions of discrete subpopulations of immune cells, including T cell subtypes such as Th17 and NK cells.
  • Bespoke assays can be developed to study the unique inflammatory and immune pharmacology of individual targets, for example eosinophil receptor signalling.

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Fibrotic diseases

Sygnature Discovery’s integrated teams of medicinal chemists, bio scientists, DMPK and translational scientists have developed significant expertise in drug discovery in the fibrosis field, with a particular focus on kidney, liver and lung fibrosis.

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Metabolic diseases

Sygnature’s scientists have extensive experience in the field of metabolic disease, from early medicinal chemistry right through to in vivo testing. The integrated teams at Sygnature Discovery have a track record of delivering validated drug candidates to clients.

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Oncology and Immuno-oncology

We have successfully delivered more than 16 pre-clinical oncology projects, utilising our Integrated Drug Discovery expertise to develop small molecule drug candidates to treat a variety of cancers such as leukaemia, breast and prostate cancer. From initial screening and profiling through to clinically relevant Biomarkers, our DMPK and bioscience group can provide full support for your discovery projects.

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Anti-Infectives

Sygnature have a history of enabling discovery success in the field of anti-infectives. Our Integrated Drug Discovery teams have worked in close collaboration with many clients to design potent and efficacious compounds. Our Bioscience team can provide cytopathic effect and viability screening assays to assess compounds designed to inhibit virus attachment, entry or replication in human host cells.

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Neuroscience

Our scientists have a well-developed understanding of the challenges associated with the design and optimisation of compounds that target the central nervous system (CNS). Our experience is both broad, reaching across a number of neurodegenerative diseases (such as Alzheimer’s, Parkinson’s and Amyotrophic Lateral Sclerosis) and neuropathic pain, and deep-rooted, with members of our senior team having 10+ years in CNS drug research.

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Respiratory

We have an excellent track record of success in the field of respiratory diseases using our extensive in-house expertise, accelerating 5 compounds to the clinic and a further 4 into preclinical development for our clients. Our collaborative approach to drug discovery and our established network of KOLs in the field have been invaluable to the progression of our clients’ projects

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Inflammation and Immunology

Our scientists have a rich heritage in this therapeutic area and provide significant experience in developing in vitro assays utilising Peripheral Blood Mononuclear Cells (PBMCs), T lymphocytes (e.g. CD4+/CD8+), leukocytes, and phagocytes, amongst others, that assess various inflammation and immunological biomarkers, processes, and endpoints.

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