De-Risking a Large Molecule Through Predictive ADME/Tox and Metabolism Profiling

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Case Study 01

De-Risking a Large Molecule Through Predictive ADME/Tox and Metabolism Profiling

A multi-model assessment of off-target effects, transporter liabilities, metabolic stability, and predicted metabolites — delivered as a single decision-ready report.

  • Large molecule
  • ADME/Tox
  • Off-target profiling
  • Metabolic stability
  • Metabolite prediction

Challenge

A pharmaceutical company held a large molecule and needed a clear picture of its potential ADME/Tox and off-target effects before committing further resources. Alongside safety and selectivity, they wanted to understand the molecule's metabolic stability and anticipate the metabolites it was likely to form — endpoints that are slow and expensive to explore experimentally up front.

What We Did

  1. 1
    MegaTox machine learning models

    Predictions across a broad set of ADME/Tox endpoints.

  2. 2
    MegaTrans machine learning models

    Drug-transporter predictions aligned to FDA guidance.

  3. 3
    MegaPredict ChEMBL models

    Binding and activity predictions for each human single-protein target drawn from the ChEMBL database.

  4. 4
    MegaPredict SafetyScreen44 models

    Virtual analogues of the SafetyScreen44 panel of safety assays.

  5. 5
    MegaPredict BindingDB Search

    Similarity-based target identification to surface likely off-target interactions.

  6. 6
    Read-across analysis

    Our implementation of the EPA ToxRef database, run in a secure environment.

  7. 7
    Metabolite prediction

    A consensus of three metabolite-predictor tools to map likely metabolic fate.

Every prediction was reported with prediction probabilities and applicability domain (AD) scores, so the team knew not just the call but how much to trust it.