ENDOCRINE DISRUPTION

Our test battery to predict endocrine disruption potential has been conceived using different methodologies (2D SARs, molecular docking and a compilation of quality third party tools) to find both positive and negative alerts for EATS endocrine pathways. It is our conviction that the majority of chemicals have no potential to cause endocrine effects. These in silico models have been created with the intent to speed up the process and lower the cost by finding cases where further experimentation is necessary and to help deprioritise the others.

KREATiS endocrine disruption potential battery is designed to predict the presence or absence of known endocrine disrupting modalities, focusing on Estrogenic, Androgenic, Thyroidal and Steroidogenic (EATS) modalities, e.g. estrogen receptor alpha agonism.

The battery is comprised of 3 steps, each using a different method to strengthen the probability of ultimately getting the right answer:

  • iSafeRat® ED SAR: our homegrown structural alerts model to predict EATS modalities
  • Third party tools: consensus of third-party models’ predictions on endocrine disruption-related endpoint
  • iSafeRat® SESAME-3D: workflow for molecular modelling engineered to combine a myriad of tools (including molecular docking and molecular dynamics) to quantitatively predict the binding affinity of substances to biological targets

The aim of this battery is to offer confident predictions of a molecule’s endocrine disrupting modality potential or, equally as important, the lack of it!

- Consensus of 3 steps
The predictions obtained via the use of the 3 steps: 2D SARs, molecular docking and a compilation of quality third party tools, are then combined for an overall prediction for each endpoint.