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Neuroscience

Neuroscience drug discovery encompasses neurodegenerative diseases and neuropathic pain, plus psychiatric conditions such as schizophrenia and substance use disorders. Developing drugs for CNS disorders has proven particularly challenging, and clinical failures are unfortunately commonplace. However, through focus on high-quality molecules, well validated in-vivo models, and applying disease understanding, the experienced team at Sygnature can ensure the best possible chances of success.

While many large pharma companies have scaled back their research in the field over the last decade, there remains a clear unmet medical need, with significant investment in neuroscience drug discovery continuing across the broader healthcare sector. Sygnature’s scientists offer an integrated neuroscience platform to support client projects in this particularly challenging therapeutic area.

Our team has deep-rooted experience in developing tailored small molecule discovery strategies across a range of target classes which are key to neuroscience therapeutics, including enzymes and GPCRs. Our established CNS-focused discovery capabilities in medicinal chemistry and DMPK are supplemented by a broad range of bioscience assay platforms and technologies.

On the in vivo side, Sygnature’s scientists have extensive expertise in the field of neuroscience, with skills that have been developed and honed over many years. Working across the breadth of the neuroscience field, our techniques include microdialysis, receptor binding studies and behavioural studies.

The Sygnature team has experience of delivering preclinical candidates for neuroscience projects. Our experts have made significant contributions to the success of several marketed drugs in the neuroscience field, and many more that have reached preclinical and clinical development

Neuroscience in vitro assay platform

  • High-content and live cell imaging platforms to support multiple CNS focused assays generating multi-parametric data from relevant cell types.
  • Bespoke assays to study and quantify neurite dynamics and structure.
  • Customisable excitotoxicity assays to identify neuroprotective agents.
  • Microglia-based assays to support neuro-inflammation based research (Phagocytosis, M1/M2 polarisation, cytokine production).
  • Phenotypic screening to support the identification of novel chemical starting points by running medium-throughput screens (MTS) up to 20K compounds in high content assays.
  • mRNA and protein expression, including intracellular signalling pathway analysis.
  • Experience in culturing immortalised and primary rodent neuronal and microglial CNS cell types.
  • Human disease iPSC-derived neurons and microglial cells, bringing research closer to the human disease state.
  • Our computational chemistry group has implemented and validated our own MPO approach to optimise the design of brain-penetrant drugs.
  • Our DMPK group provides advice on relevant assays and tissue distribution studies to assess potential for drug exposure and target engagement in the CNS.

Our biological sciences department provide bespoke in-vivo models to evaluate CNS pharmacodynamic and efficacy endpoints across a range of neurological and psychiatric indications including substance use disorders, schizophrenia, binge eating disorder, and Parkinson’s Disease.

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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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