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Fibrotic diseases

Fibrosis is a process of pathological wound healing, when normal parenchymal tissue is replaced by connective tissue including collagen. Fibrosis thus induces tissue remodelling with the formation of a scar tissue, which interferes with or totally inhibits the normal architecture and function of the underlying organ or tissue.

The condition can affect any organ such as liver, kidney, lung or heart, among many others. Even though the fibrotic lesions tend to be focal on individual organs, the cascade that triggers fibroblast activity is fairly conserved across tissues. While fibrosis is a key driver of end stage organ damage and death in a variety of chronic diseases, no treatments to halt or reverse the lesions are currently available.

Sygnature Discovery’s integrated teams of medicinal chemists, bioscientists, 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.

As well as having access to a range of ready, validated in vitro assays for fibrosis using liver and kidney fibroblasts, our bioscientists are skilled in developing bespoke assays for individual projects that precisely meet the needs of clients’ drug discovery efforts, regardless of the target organ.

Additionally, we offer a range of translational models to evaluate novel therapeutics for the treatment of fibrosis, these include the adriamycin model of kidney fibrosis with associated readouts and the CD, H-FFC, ob/ob H-FFC, and H-FFC CCl4 mouse which develop liver fibrosis alongside NASH.

Fibrosis Assays

Rat Kidney Cell TGF-β Fibroblast to Myofibroblast Transdifferentiation (FMT) Assay (inhibition and reversal modes). High-content imaging and RT-qPCR readouts.

Primary Human Hepatic Stellate Cell TGF-β Fibroblast to Myofibroblast Transdifferentiation (FMT) Assay (inhibition and reversal modes). High-content imaging and RT-qPCR readouts.

Fibrosis Models

In vivo models of kidney fibrosis. Adriamycin-induced model of focal segmental glomerulosclerosis (FSGS) and fibrosis

Dietary induced models of liver fibrosis and NASH. Choline deficient (CD) mouse, high-fat high-fructose high-cholesterol (H-FFC) mouse, ob/ob H-FFC and H-FFC CCl4.

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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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