Sygnature Discovery > Neuroscience

Neuroscience

Sygnature Discovery has significant scientific expertise across multiple disciplines in the fields of neurodegenerative disease and neuropathic pain, with several members of our senior team having substantial experience in CNS disease research.  This combined experience has resulted in the delivery of two preclinical compounds in the neurodegenerative area and has embedded the knowledge and skill sets required to support neuroscience research projects across the discovery pipeline.

Developing drugs targeting the CNS presents some additional hurdles to systemic delivery and frequently takes longer to deliver clinical POC. This, together with many well publicised clinical late-stage failures in recent years, has led to many large pharma to scale back research in this area. Nevertheless, there is a large unmet need in our ageing population and new drugs continue to be approved for clinical use in the neuroscience area.  Sygnature Discovery has responded to address this issue by developing a neuroscience platform to help support client projects in this challenging therapeutic area.

Our scientists have deep-rooted experience in developing tailored small molecule discovery strategies across the range of target classes which are key to neuroscience therapeutics, such as enzymes and GPCRs. Our established CNS-focused discovery capabilities in our Chemistry and DMPK departments are supplemented by a broad range of assay platforms and technologies available via our Bioscience Department.  Sygnature’s capabilities continue to expand via collaborations with innovative clients such as our projects with Keapstone Therapeutics and Parkinson’s UK, focused on discovering new treatments for Parkinson ’s Disease and ALS.

We offer clients a host of tailored and flexible solutions with the field of neuroscience that are specifically designed to address the scientific questions important to your research, these include:

  • High-content and live cell imaging platforms to support multiple CNS focused assays generating multi-parametric data from rare 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).
  • We offer 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 phenotypes, bringing research closer to the human disease state.
  • Our Computational Chemistry group have implemented and validated our own MPO program to help in the design of brain penetrant drugs.
  • Our DMPK group provide advice on relevant assays and tissue distribution studies to assess potential for target engagement in the CNS.

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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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Diabetes

Diabetes is a metabolic disorder that is an increasingly prevalent disease worldwide. We have established assays to support the investigation of diabetic therapies including relevant functional assays. We also have access to tissue and blood from in vivo diabetic models through strategic collaborations.

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Orphan Disease

Sygnature’s team of scientists have a strong track record of adding value to client projects in the field of rare and orphan diseases.  Sygnature’s advanced intellectual input and established relationships with providers of diseased tissue allows rapid progression of projects in this challenging therapeutic area.

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Anti-Infectives

Sygnature have a history of enabling discovery success in the field of anti-infectives. Our Medicinal Chemistry and Computational Chemistry teams have worked in close collaboration with many clients to design potent and efficacious compounds, resulting in the delivery of two preclinical candidates. 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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