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  • Integrated Drug Discovery

    Integrated Drug Discovery

    Overview

    We deliver truly integrated drug discovery programs. Our co-located teams accelerate compounds from target ID to candidate.

  • Target Identification & Validation

    Target Identification & Validation

    It’s important to lay strong foundations for successful drug discovery at this first stage of the process. Our integrated target identification and validation platform combines AI with expert insights, and rigorous lab validation to guide targets through robust evaluation, ready for hit discovery.

  • Hit Identification

    Hit Identification

    Validated, high-quality hits, delivered through integrated technologies and expert collaboration, give you a confident starting point for faster drug discovery.

  • Hit-to-Lead

    Hit-to-Lead

    High-quality hits with early proof of concept are de-risked and profiled, ready to accelerate your program towards lead optimization.

  • Lead Optimization

    Lead Optimization

    Turning promising leads into clinical candidates with speed, precision, and the scientific expertise to generate high-quality data and deliver real patient impact.

Featured Resources

  • Modalities

    Modalities

    Overview

    Delivering integrated, modality-agnostic drug discovery to tackle complex biology, accelerate development, and advance innovative therapies with confidence.

  • Small Molecules

    Small Molecules

    Expert small molecule discovery from target ID to scale-up, delivering candidates designed for success and market impact.

  • Peptides

    Peptides

    Transforming complex peptide concepts into next-generation therapies through integrated design, advanced analytics, and collaborative end-to-end discovery expertise.

  • Targeted protein degradation

    Targeted protein degradation

    Leveraging induced proximity and CHARMED technology to rapidly design, test, and optimize degraders for previously ‘undruggable’ targets.

  • ADCs

    ADCs

    Advancing next-generation ADCs through payload-focused design, integrated expertise, and collaborative innovation to deliver safer, more selective therapies.

  • Biologics

    Biologics

    Driving biologics innovation through integrated design, structural biology, and multidisciplinary expertise to accelerate next-generation therapies from concept to clinic.

Featured Resources

  • Therapeutic Areas

    Therapeutic Areas

    Overview

    Combining deep therapeutic expertise with translational insight to design strategies, reduce risk, and accelerate discovery programs toward clinical success.

  • Oncology and Immuno-Oncology

    Oncology and Immuno-Oncology

    Accelerating oncology drug discovery through integrated expertise, innovative modalities, and translational insight to deliver candidates with real clinical impact.

  • Inflammation and Immunology

    Inflammation and Immunology

    Driving immunology and inflammation drug discovery through tailored assays, translational models, and integrated expertise for faster clinical success.

  • Neuroscience

    Neuroscience

    Advancing CNS drug discovery through integrated models, translational biomarkers, and multidisciplinary expertise to overcome complexity and accelerate therapeutic innovation.

  • Metabolic Diseases

    Metabolic Diseases

    Designing and advancing differentiated small-molecule therapies for obesity and diabetes through integrated expertise, mechanistic insight, and translational strategies.

Featured Resources

  • CellCentric Lead Optimisation Campaign - CCS1477

    CellCentric Lead Optimisation Campaign - CCS1477

    Inobrodib, an exciting, first-in-class oral anti-cancer drug in clinical development by CellCentric, was collaboratively designed, synthesised and supported on its pre-clinical journey by an integrated project team at Sygnature Discovery. Inobrodib is now showing promising results in Phase I and II trials for multiple myeloma and other cancer types.

    Case study
  • About Sygnature

    About Sygnature

    At Sygnature Discovery, we deliver world-leading drug discovery solutions to accelerate your compound from idea to clinic.

  • Meet our Team

    Meet our Team

    Our leadership team brings diverse experience and insight, driving collaboration and innovation across drug discovery.

  • Careers

    Careers

    Explore careers at Sygnature Discovery and join a global team committed to science, collaboration, and integrity.

Technical Notes

CYP Induction

About the Assay

Sygnature Discovery’s CYP Induction assay provides a robust in vitro platform for determining the potential of test compounds to induce key cytochrome P450 isoforms – CYP1A2, CYP2B6 and CYP3A4 – in HepaRG™ cells. These cells retain functional AhR, CAR and PXR signalling pathways, ensuring physiologically relevant induction responses. By using FDA-recommended positive controls – Omeprazole (CYP1A2), Phenobarbital (CYP2B6) and Rifampicin (CYP3A4) – the assay reliably detects transcriptional upregulation via RT-qPCR measurement of mRNA. This approach offers valuable mechanistic insight early in drug development, allowing assessment of potential drug–drug interactions and metabolic liabilities before clinical studies. The assay is designed to provide consistent, reproducible performance across experiments, and its use of human-derived HepaRG™ cells ensures high biological relevance.

Protocol Summary

The assay begins with the seeding of HepaRG™ cells onto collagen-coated 96-well plates, followed by an incubation period to allow the cells to stabilise. After initial culture, the medium is replaced with serum-free induction medium containing test compound. Test compound and positive control inducers are added across a defined concentration range in triplicate. Following a 24-hour exposure period, cells are lysed and total mRNA is extracted. Gene expression levels for CYP1A2, CYP2B6 and CYP3A4 are quantified using RT-qPCR, and fold-induction values are calculated relative to vehicle controls using established comparative Ct methods. The workflow is optimised to maintain consistency between runs and to support both intra- and inter-assay reproducibility.

Validation Results

Validation demonstrated highly consistent induction responses for all three CYP isoforms. For CYP1A2 with 50 µM Omeprazole, mean 26.3 fold induction was observed. Intra-assay CVs ranged from 6.82% to 13.7%, with an inter-assay CV of 15.0%. CYP2B6 induction by 1000 µM Phenobarbital, mean 15.0 fold induction was observed with intra-assay CVs between 3.82% and 14.9%, and an inter-assay CV of 30.6%. CYP3A4 induction using 10 µM Rifampicin showed a mean fold induction of 64.8, with intra-assay CV values of 9.85% to 38.4% and an inter-assay CV of 16.4%. These data confirm a highly reliable and sensitive assay system capable of detecting transcriptional activation across diverse inducer mechanisms.

Resources

Related Research & Resources

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