Tier 2: Long Term (14 days) | InSphero

DILI Prediction

Tier II: Long-term (14 days)

Ensure highest sensitivity for DILI drugs with long-term exposure

In our experience working with long-lived 3D human liver microtissue models, exposure to clinically known DILI compounds is best predicted using a 14-day dosing regimen. Using a 110-compound validation set, we observed up to 2-fold higher sensitivity for detection of clinically known DILI drugs than with conventional 2D hepatocyte culture.

  • Double sensitivity in DILI prediction without sacrificing specificity using an organotypic, metabolically robust, long-lived spheroid model validated with a set of 110 clinically defined DILI compounds
  • Reduce late-stage market withdrawal liability by leveraging a high positive predictive value (sensitivity) that correctly predicted 18 known DILI drugs (black box or discontinued) missed by 2D primary human hepatocyte (PHH) cultures of the same hepatocyte donor
  • Retain more blockbusters in your pipeline with a high negative predictive value (>92% specificity) that ensures valuable drugs aren’t prematurely discarded as with low specificity (60-90%) models

Example Data

3D InSight™ Liver Microtissues capture DILI responses to compound exposure that other in vitro models miss.

Compounds with clinically defined DILI severity (1 = severe, 2 = high concern, 3 = low concern) predicted [+] or missed [-] by 3D InSight™ Human Liver Microtissues and 2D PHH from the same donor lots.

These data are from Proctor et al. (Arch Toxicol, 2017), a collaborative study conducted by AstraZeneca, Genentech, and InSphero using 3D InSight™ Human Liver Microtissues.

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Brochure: Human Liver Microtissues

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Brochure: Solutions for Toxicology

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Poster: Drug Safety Assessment with Liver Microtissues

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