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.