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Biochemistry

An automation-enabled screening platform, applicable to both screening and mode-of-action studies, delivering robust, reliable data with rapid turnaround times.

Why Arctoris?

Automated Experimental and Analytical Pipelines

  • Unmatched experimental design potential: use of non-contact digital and positive displacement dispense capabilities delivers exquisite resolution.
  • Comprehensive protocol encoding: ensures unparalleled reproducibility, capturing and reporting all experimental data and relevant metadata.
  • Seamless integration: minimizes cycle times and costs while maintaining sector-leading data resolution and confidence
  • Custom pipelines: enable development of personalized proposals tailored to the research project.

Hit identification and Molecular triangulation

  • Precision automation: ensures lower variability supporting reduced risk of false negatives while accelerating project progression and unlocking potential to profile 1,000s of molecules against 100s of targets.
  • Proprietary hit identification methodologies: delivers potency profile for every molecule tested, ensuring requirements for machine learning as well as traditional drug discovery activities can be fully supported.
  • Outputs used to generate focused, asymmetrical titrations, providing greater confidence in and ability to resolve parameters for different molecules (e.g. affinity, existence of multiple binding sites etc.).

Detailed Mechanistic Characterization

  • Integrated network of coded experimental and analytical processes used to assess catalytic/inhibitory interactions.
  • Exploiting automation to deliver consistency, accuracy and precision required, earlier in the drug discovery process, and at scale.
  • Experimental designs supported by empirical theory, data simulations and detailed modelling.
  • Temporal readouts used to extract rate constants (association/ dissociation); two-dimensional experimental arrays used to elucidate mechanism of inhibition (e.g. substrate competitive) and potential synergistic interactions between molecules (as per Yonetani-Theorell)

What can Arctoris do?

Our capabilities and assays

Screening

Precisely quantify drug potency and selectivity
  • High-throughput screening
  • Focused screening sets (kinases inhibitors, DDR, cell cycle, etc.), fragment libraries, macrocycles
  • Independent, non-contact responsive curves
  • Non-serial, uniform, or asymmetrical dosing can all be accommodated
  • Fully automated experimental protocols and analytical pipelines
  • Industry-leading precision and consistency builds maximum confidence

Equilibrium-based Profiling

Assess relative potency with real confidence
  • Digital, picolitre precision of compound handling
  • Per-compound individualised experimental designs
  • Rapid selectivity profile construction
  • Full spatial randomization
  • Internal controls & technical replication
  • Catalytic and binding readouts
  • Coupled and direct detection systems
  • Protein-protein interaction assays

Kinetics-based Profiling

Assess relative potency with temporal insight

  • Non-equilibrium potency
  • Molecule stratification for detailed follow-up
  • Enhanced selectivity/ liability profiling
  • Detection of kon/koff/kinact
  • Cluster or differentiate lead series according to kinetic profile
  • Characterise covalent inhibition
  • Contrast isolated target vs in-cellulo target engagement kinetics (NanoBRET)

Mechanism of Action

Determine mode of inhibition or activation, competition or synergy
  • Determine and quantify mode of drug action
  • Distinguish competitive vs. uncompetitive vs. noncompetitive modes of action
  • Evaluate drug combinations for synergy
  • Confirm and characterise cellular target engagement
  • Build theoretical models and simulations and validate experimentally to determine complex rate constants and modes of action

How do we deliver?

  • Our Ecosystem of Excellence of suppliers allows us to access highest quality assay components (targets, substrates, detection systems, molecules), seamlessly integrating with our internal protein sciences team for custom reagent production
  • To ensure robust assay performance, all reagents undergo proof-of-performance testing where by functional validation of reagents and target proteins are assessed and compared to expected performance metrics/ protocols
  • In finalizing onboarding, we confirm and optimize the assay’s key parameters (protein/ substrate dependencies, reaction linearity/ signal stability) with our high performance thresholds (robust Z’, pharmacological standards, outlier numbers).

 

  • One of our patented approaches to enhance experimental efficiency is molecular triangulation, wherethe potency of focused libraries and fragment sets is triangulated while assigning confidence in our estimated potency. This reduces the required spend on hit follow up screening and improves confidence that false negatives will not be carried through to the next stage in hit identification.
  • Our automated research platform also allows us to support molecular profiling led by ML predictions or traditional medicinal chemistry, with serially-spaced or targeted concentration response curves focusing on key parameters such as IC50, Hill slope, maximum asymptote etc.
  • With advanced automated analysis pipelines we are able to perform rigorous unbiased 4-parameter logistic analysis (IC50), Schild regression analysis (effects of agonists and antagonists on ligand-receptor binding) and multisite binding (cooperativity), providing you with fully analysed and annotated datasets.
 
  • In order to gain a detailed understanding of compounds, indicative mechanistic profiling which involves temporal IC50 profiling identifies molecules with potentially differentiated binding and unbinding rates. Conditional IC50 profiling also identifies modes of inhibition relative to substrates, cofactors, etc.
  • This form of detailed mechanistic assessment involves global progress curve analysis aligned with independent kinetic model assessments.